See the embryonic expression pattern of bun at the Berkeley Drosophila Genome Project Patterns of Gene Expression Site
bunched is expressed in a hedgehog-dependent stripe in the undifferentiated cells just anterior to the morphological furrow of the eye imaginal disc. It appears to be involved in the transmission of the differentiation-inducing signal; a reduction in bunched function leads to a delay in differentiation and to a loss of photoreceptors in the adult. bunched is also required for a morphogenetic movement in the brain that reorients the second optic lobe relative to the first. Input from the eye is required for this rotation. Additional functions of shs include a role in wing margin development and a requirement for both male and female fertility (Treisman, 1995).
The mutant is lethal, but a few surviving adults have slightly small, rough eyes. The first observable phenotype evinces a delay in neural differentiation. The mutation is enhanced by a single copy of hedgehog or decapentaplegic. The mutant phenotype is suppressed by the loss of one copy of wingless (Treisman, 1995).
In the follicle cell (FC) epithelium that surrounds the Drosophila egg, a complex set of cell signals specifies two cell fates that pattern the eggshell: the anterior centripetal FC that produce the operculum and the posterior columnar FC that produce the main body eggshell structure. The long-range morphogen DPP represses the expression of the bunched (bun) gene in the anterior-most centripetal FC. bun, which encodes a homolog of vertebrate TSC-22/GILZ, in turn represses anterior gene expression and antagonizes Notch signaling to restrict centripetal FC fates in posterior cells. From a screen for novel targets of bun repression, the C/EBP homolog slow border cells (slbo) has been identified. At stage 10A, slbo expression overlaps bun in anterior FC; by stage 10B they repress each other's expression to establish a sharp slbo/bun expression boundary. The precise position of the slbo/bun expression boundary is sensitive to Notch signaling, which is required for both slbo activation and bun repression. As centripetal migration proceeds from stages 10B-14, slbo represses its own expression and both slbo loss-of-function mutations and overexpression approaches reveal that slbo is required to coordinate centripetal migration with nurse cell dumping. It is proposed that in anterior FC exposed to a Dpp morphogen gradient, high and low levels of slbo and bun, respectively, are established by modulation of Notch signaling to direct threshold cell fates. Interactions among Notch, slbo and bun resemble a conserved signaling cassette that regulates mammalian adipocyte differentiation (Levine, 2007).
bunched refines a DPP activity gradient by antagonizing Notch signaling to establish the posterior edge of the operculum-forming centripetal FC. This study reveals that bunched is part of an intricate switch reliant on Notch activation of slbo to direct alternate FC fates. These observations contribute to a model in which bunched connects long-range morphogen cues to short range, cell contact-dependent signaling. Together with recent work on the bunched homologue GILZ in mammalian cell culture, these data suggest that this family of proteins is part of a conserved signaling cassette regulating cell fate decisions, as detailed below (Levine, 2007).
In different contexts cells migrate either as integrated sheets, such as during convergent extension, or as small groups of cells, such as during neural crest migration. During border cell migration from stages 8-10, a subset of anterior FC transiently loses epithelial polarity, delaminates and rounds into a small semi-polarized cell cluster that migrates through the nurse cell complex. In contrast, during centripetal migration from stages 10-14 a ring of anterior follicle cells changes shape and squeezes through the oocyte/nurse cell complex in a process coordinated with rapid nurse cell dumping. Marker gene expression indicates that the centripetal FC stretch to cover the anterior of the oocyte and retain epithelial contacts with the anterior and posterior nurse cell FC and columnar FC groups, respectively, throughout this mass cell ingression. While unique genetic pathways likely regulate these distinct cell migrations, because both the border cells and the centripetal FC coordinately migrate through the germ line cyst and arrive in the same vicinity at the anterior of the egg, it is unsurprising that common components are involved in both processes. Non-muscle myosin (zipper) and DE-cadherin (shotgun) are expressed and required for migration in both cell types. As well, it has been shown that slbo itself is required for DE-cadherin accumulation during both border cell and centripetal FC migrations, an observation consistent with the role for slbo function in the centripetal FC that are demonstrated in this study. Recently, screens for border cell-specific gene expression have identified many transcripts expressed in both tissues (Levine, 2007).
Comparing the role and regulation of slbo during the centripetal FC sheet and border cell cluster migrations reveals both shared and unique requirements. Weak slbo mutations, which completely block border cell migration, have no discernable effect on centripetal FC migration, which is disrupted only in stronger allelic combinations. While early slbo mutant clones reduced DE-cadherin accumulation in the dorsal anterior FC and in the border cells, late slbo mutant clones in the nurse cell FC and centripetal FC are difficult to recover and properly stage. These clones result in several effects on late stage egg chambers. First, these resulted in increased levels of DE-cadherin and decreased levels of DLG consistent with changes in epithelial polarity and adhesion. Second, large anterior slbo mutant clones are associated with a failure of centripetal FC ingression to coordinate with nurse cell dumping. It is noted that slbo mutant phenotypes are distinct from DE-cadherin shotgun (shg) mutants, which result in ectopic centripetal migration between posterior nurse cells. slbo mutants do resemble dlg mutant phenotypes associated with defects in FC shape and epithelial invasiveness. And third, ectopic slbo-lacZ expression associated with disintegration of the follicular epithelia and egg chamber collapse which are likely connected to defects in epithelial maintenance. Thus previous reports that the strong slbo allele has no effects on centripetal FC migration may result from difficulties recovering and staging these highly aberrant and friable late stage mutant egg chambers (Levine, 2007).
The mechanism of slbo regulation in the border cells and centripetal FC is also distinct. It has been shown that post-transcriptional regulation of slbo protein levels is critical to proper border cell migration but does not occur in the centripetal FC. This study shows that in both cell groups, Notch initiates slbo expression and slbo is necessary and sufficient to repress its own expression as centripetal migration proceeds. SLBO protein can bind to a DNA sequence element located near the start site of its own promoter, and several matches to the canonical C/EBP binding site occur as well in the sequence of the slbo2.6 element that is sufficient to mediate autorepression, so this regulation is likely direct. Thus slbo adopts two strategies to fine-tune its levels: post-transcriptional regulation specifically in the border cell and transcriptional autoregulation in the both cell groups, as shown in this study (Levine, 2007).
It has been shown that DPP establishes the position of the bun expression boundary in the anterior FC and this boundary coincides with the posterior edge of the operculum eggshell structure. This study shows that as this boundary forms, slbo and bun expression patterns initially overlap and subsequently slbo and bun repress each other's expression to resolve respective expression patterns into two distinct cell groups. Notch signaling plays a central role in these interactions: Notch activates slbo expression in the centripetal FC and bun is required to antagonize Notch activation in posterior cells adjacent to the boundary (Levine, 2007).
The position of the boundary is highly sensitive to Notch activity so that increased Notch signaling leads to increased slbo2.6 expression both in the centripetal FC and, surprisingly, in adjacent columnar FC. Ectopic slbo expression in Nintra-expressing columnar FC at stage 10B is not associated with changes in FC proliferation and thus the spread of Notch activity likely relies on cell–cell signaling. This may arise either from (1) Notch activation of slbo expression in a large group of centripetal FC precursors that is not subsequently downregulated to a more narrow domain or (2) a Nintra-dependent activation of Notch signaling in adjacent columnar FC leading to cell contact-dependent posterior spread of slbo expression. The latter explanation is preferred because slbo2.6GAL4 expression expanded to almost all columnar FC in many egg chambers. In this way the position of the DPP-dependent cell fate boundary that defines the operculum is quite flexible but always drawn sharply by Notch activation (Levine, 2007).
While several canonical bun and Suppressor of Hairy [Su(H)] binding sites are located in the slbo2.6 element indicating slbo regulation by bun1 and Notch signaling, respectively, might be direct, several observations indicate slbo regulation at the boundary by bun is likely more complex. It has been noted previously that: (1) high levels of Notch and Notch target gene expression occur in anterior FC, with slightly reduced levels in centripetal FC in contact with bun-expressing cells and (2) increased levels of Notch targets occur in all cells of bun mutant clones at the centripetal FC boundary except those that contact bun+ cells. A parallel relationship is observed between bun and the Notch target slbo: (1) reduced levels of slbo occur in cells adjacent to bun-expressing cells in WT egg chambers, and (2) slbo expression occurs in bun mutant clones located at the centripetal FC boundary, with lower slbo levels in bun− cells in contact with bun+ cells. Thus while bun may repress slbo directly, bun also antagonizes Notch activation of slbo in a non-cell autonomous manner. Consistent with this, bun clones removed from the centripetal FC do not lead to increased slbo expression and bun1 is not sufficient to block Nintra activation of slbo2.6 in the centripetal FC (Levine, 2007).
Notch modulation of slbo expression may be indirect as well. Because the Nts; slbo01310/slbo01310 double mutant egg chambers retain strong slbo-lacZ expression throughout the FC compared to Nts; slbo01310/+ egg chambers stained in parallel, it is hypothesized that Notch blocks SLBO protein's ability to repress its own expression. In this scenario, which must be further tested, the rapid reduction in slbo expression as centripetal migration proceeds results from both (1) decreasing Notch activation of slbo via Su(Hw) sites in the slbo promoter and (2) relief of a block on slbo autorepression. Consistent with rapid changes in Notch levels in the migrating centripetal FC, as slbo levels decrease a corresponding increase is seen in the levels of Cut protein, a key target of Notch repression in these cells. Because reduced dorsal appendages and opercula are seen in Nintra-expressing egg chambers, it is likely that rapid reduction in Notch levels is critical to permit the further patterning of anterior structures (Levine, 2007).
Dynamic interactions among bun, slbo and Notch signaling tightly regulate DE-cadherin levels in the centripetal FC. bun mutant clones lead to increased Notch signaling and DE-cadherin accumulation and Nintra is sufficient to increase DE-cadherin levels in the FC. slbo mutant clones lead to loss of DE-cadherin expression early and ectopic DE-cadherin levels late. Thus a recurring theme is that tight modulation of DE-cadherin levels is required in the FC at late oogenesis for epithelial transitions including border cell migration, centripetal FC migration and dorsal appendage elongation (Levine, 2007).
Recently, it has been shown that the bun homolog GILZ antagonizes the ability of C/EBP to activate expression of the key fat cell master regulator gene PPARγ2 (Peroxisome Proliferator Activator γ2) in adipogenic mesenchymal stem cells (Shi, 2003). GILZ binds a promoter element required for C/EBP-mediated activation and recruits HDAC1 (Histone Deacetylase 1) to repress PPARγ2 expression and promote the osteogenic cell fate. GILZ can also directly bind to C/EBP in vitro. Shi (2003) proposes that a balance of GILZ repressor and C/EBP activator in precursor mesenchymal cells regulates levels of PPARγ2, the master fat cell regulator. The similarities between these pathways are striking and it is proposed they constitute a conserved signaling cassette required for cell fate commitment. In support of a role for Notch in both, it has been shown that Notch signaling promotes adipogenesis in tissue culture , although the specific role of Notch in adipogenesis has been questioned. Targets may be conserved as well: expression of a gene homologous to PPARγ2 in the centripetal FC has been noted. While a connection between border cell specification and adipogenesis has been noted, slbo has no role in fly fat body formatio. However, bun expression hduring fat body formation has been detected suggesting that portions of this fly signaling cassette may operate in a general pathway required for storage cell differentiation (Levine, 2007).
The bunched (bun) gene encodes the Drosophila member of the TSC-22/GILZ family of leucine zipper transcriptional regulators. The bun locus encodes multiple BUN protein isoforms and has diverse roles during patterning of the eye, wing margin, dorsal notum and eggshell. This study reports the construction and activity of a dominant negative allele (BunDN) of the BUN-B isoform. In the ovary, BunDN expression in the follicle cells (FC) results in epithelial defects including aberrant accumulation of DE-cadherin and failure to rearrange into columnar FC cell shapes. BunDN expression in the posterior FC leads to loss of epithelial integrity associated with extensive apoptosis. BunDN FC phenotypes collectively resemble loss-of-function bun mutant phenotypes. BunDN expression using tissue-specific imaginal disk drivers results in characteristic cuticular patterning defects that are enhanced by bun mutations and suppressed by co-expression of the BUN-B protein isoform. These data indicate that BunDN has dominant negative activity useful to identify bun functions and genetic interactions that occur during tissue patterning (Ash, 2007).
The bunched (bun) gene encodes the fly member of the TSC-22/GILZ/BUN family of proteins whose structures share conserved leucine zipper and DNA binding motifs. Several lines of evidence indicate that these proteins act as transcriptional regulators: (1) GILZ has been show to be a sequence-specific DNA binding protein with histone deacetylase-dependent transcriptional repressor activity in tissue culture cells (Shi, 2003); (2) TSC-22 has activator and repressor functions, depending on the method of assay; and (3) bun is a potent repressor of gene expression in migrating ovarian cells (Ash, 2007).
TSC-22 and GILZ both function in sundry developmental processes linked to cell differentiation, cell growth and migration. GILZ mediates glucocorticoid (GC)-stimulated tissue differentiation including T-cell maturation (Asselin-Labat, 2004; Ayroldi, 2002; Berrebi, 2003; Cohen, 2006; Mittelstadt, 2001; Riccardi, 2001), stem cell maintenance (Kolbus, 2003), and adipogenesis (Shi, 2003). TSC-22 is widely expressed in the early mouse embryo (Dohrmann, 1999, Kester, 1999) and in adult tissues including the mouse hair follicle, chick feather bud tract, and human colon and erythyroid cell lineages (Choi, 2005; Dohrmann, 2002; Gupta, 2003; Soma, 2003). Misexpression of TSC-22 in cell culture leads to cell type-specific effects on growth and apoptosis (Hino, 2002; Ohta, 1997; Shostak, 2003; Xu, 2003). Conversely, RNAi knockdown of Xenopus TSC-22 increases cell division and delays embryonic blastopore closure (Hashiguchi, 2004). These outcomes support the notion that TSC-22 links cell proliferation and tissue morphogenesis and consistent with this, TSC-22 has tumor suppressor properties in several cancer cell types (Iida, 2005; Rentsch, 2006; Shostak, 2005; Ash, 2007 and references therein).
Deletion of the N- and C-terminal domains of TSC-22 required for transcriptional regulation generates a mutant version (DN-TSC-22) that exhibits dominant negative properties in tissue culture (Gupta, 2003). This study demonstrates that a corresponding derivative of the BUN-B protein has dominant negative properties during the patterning of several adult tissues (Ash, 2007).
A requirement for bun has been demonstrated in cells that contact the centripetally migrating FC in the ovary: in bun mutant clones that contact the boundary of the centripetal migrating FC increased expression of Notch target genes is observed and accumulation of several cell junction proteins including DE-CAD, DLG and ARM (Dobens, 2005; Levine, 2007). This study shows that similarly, Flp-out clones expressing BunDN in anterior FC that contact the centripetal FC resulted in cell autonomous increases in accumulation of DE-cadherin (DE-CAD). The similarity between BunDN-expressing FC clones and bun loss-of-function clones argues strongly that BunDN blocks bun activity in these cells. Effects of BunDN expression in the FC suggest other unreported roles for bun in FC patterning. In large anterior BunDN clones, cells fail to rearrange and flatten to form stretch FC at stage 10 apparently leading to a collapsed egg chamber phenotype. In posterior FC, BunDN clones result in a striking loss of epithelialization of the follicle cell layer. This latter phenotype resembles that of bun mutant clones that lose adhesion to the posterior of mutant egg chambers. The loss of epithelial polarity in posterior FC found in both bun loss-of-function clones and in clones expressing BunDN correlates with increased levels of DE-cadherin, DLG and ARM throughout the clone and increased TUNEL staining in some cells of the clone. A role for BUN in apoptosis parallels the requirement for GILZ in apoptotic protection of IL-2 starved T-lymphocytes and suggests a conserved role for these genes in hindering cell death (Ash, 2007).
From a screen of imaginal disk GAL4 drivers it was shown BunDN expression interferes with cuticle patterning in the eye and notum. In the notum, a pnr-dependent notum cleft phenotype was enhanced by both BunDN expression and bun loss-of-function alleles; conversely the cleft phenotype was suppressed by BUN-B. BunDN effectively blocked the latter BUN-B suppression phenotype. In stronger mutant combinations – such as bun-pnr- double mutants and the PnrGAL4>3xUAS-BunDNHA genotype – a significant increase was observed in the abundance of notum bristles and defects in their polarity. The opposing effects of gain- and loss-of-bun activity on pnr phenotypes suggest that bun functions normally in the pnr pathway to (1) promote the spreading and fusion of the dorsal wing disc epithelium required for proper notum formation and (2) limit bristle formation. The interaction between bun and pnr suggests that a balance of these factors is required to pattern this tissue, and consistent with this, pnr and bun reporter genes have overlapping expression in the dorsal notum of the wing disk primordia (Ash, 2007).
In a second key assay of BunDN activity, the OmbGAL4 driver was used to test BUN-B and BunDN interactions at the forming wing margin. BunGAL4 expression occurs in cells flanking the wing margin indicating that bun normally restricts Notch activity to the margin and in support of this, both weak bun mutations and expression of BunDN resulted in wing notch phenotypes. OmbGAL4 expression of BUN-B in distal wing margin cells resulted in strong wing notch phenotypes that correlated with repression of the Notch target WG at the distal margin of the wing pouch. BunDN coexpression with BUN-B at the margin effectively reduced BUN-B wing notches and increased WG levels in the wing pouch. BunDN overexpression leads to increased Notch activity at the margin and is associated with wing overgrowth, which has been cited as a consequence of Delta overexpression in the wing. The previous observation that bun antagonizes Notch signaling in the FC and the observation here that BunDN blocks BUN-B repression of Notch signaling at the forming margin points to a common mechanism by which bun regulates Notch signaling during tissue patterning. This notion fits a speculative model that the TSC-22/GILZ/BUN family of genes has a conserved role for in regulating Notch signaling (Ash, 2007).
Because other drivers that are expressed at the distal margin, such as DppGAL4 or PtcGAL4, gave no phenotype in combination with BunDN or BUN-B (not shown), it was surmised either that the OmbGAL4 driver is significantly stronger than those drivers, or that the OmbGAL4 insertion sensitizes distal cells to changes in BUN levels. Consistent with the latter possibility, the Omb insertion results in a wing margin phenotypes that can be suppressed by the bun alleles bun6903 and bun4230 (data not shown), indicating that bun and Omb have opposing activities during wing margin patterning. bun interactions with Omb are likely complex: Optomotor blind (Omb) gene, which encodes a T-box sequence, is regulated by Dpp and WG signals, and Omb mutants show a loss of Dpp signaling, increased Notch expression, and both apoptosis of the central wing blade cells and cell proliferation in lateral cells (Ash, 2007).
While both increases and decreases in bun levels have opposing effects on BunDN phenotypes in the wing, notum and eye, in some cases BunDN mutant phenotypes resulted only from expression of multiple copies of the transgene. It is notable that in Westerns of ovarian protein extracts expressing BunDN, increased level of several high molecular weight species were detected that cross-reacted with BUN antisera. Some of these species correspond in size to BUN-B and BUN-A proteins. Such an outcome suggests that BUN might repress its own expression normally and may explain why driving BunDN expression by BunGAL4 and hsGAL4 led to only mild cuticular phenotypes. The BUN-B homolog GILZ is thought to repress its own expression by transcriptional repression of its activator FoxO3 indicating that bun autoregulation may be conserved (Asselin-Labat, 2005). Previously bun was shown to repress Serrate levels in the FC, so the observation that SerrateGAL4 driving expression of BUN-B or BunDN resulted in no wing patterning defects (not shown) may be explained by feed back modulation of the expression of this driver. Thus interpreting the effect of BunDN on patterning is subject to complexities such as (1) bun autoregulation, (2) cross-regulation of transcription of the driver promoter and (3) genetic interactions between reduced bun activity and the driver insertion (Ash, 2007).
Recent sequencing efforts have identified three new bun splice isoforms that, in addition to BUN-A, -B and -C, represent a set of at least six BUN proteins that can interact to form heterodimers via a common leucine zipper structure encoded by a shared 3'exon. Preliminary data indicates that complex, overlapping expression patterns of the six Bun RNA isoforms occurs in the FC. Thus resolving the developmental contribution of specific BUN isoforms will be aided by a tool like BunDN, which can be used to compare tissue-specific 'targeted blockade' of bun activity and with the effects of isoform add-back (Ash, 2007).
Search PubMed for articles about bunched
Ash, D. M., Hackney, J. F., Jean-Francois, M., Burton, N. C. and Dobens, L. L. (2007). A dominant negative allele of the Drosophila leucine zipper protein Bunched blocks bunched function during tissue patterning. Mech. Dev. 124(7-8): 559-69. PubMed citation: 17600691
Asselin-Labat, M. K,m et ak, (2004), GILZ, a new target for the transcription factor FoxO3, protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis. Blood 104: 215-223. PubMed citation: 15031210
Ayroldi, E., et al. (2002). Glucocorticoid-induced leucine zipper inhibits the Raf-extracellular signal-regulated kinase pathway by binding to Raf-1. Molec. and Cell. Biol. 22: 7929-7941. PubMed citation: 12391160
Berrebi, D., et al. (2003). Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10. Blood 101: 729-738. PubMed citation: 12393603
Biemar, F., et al. (2006). Comprehensive identification of Drosophila dorsal-ventral patterning genes using a whole-genome tiling array. Proc. Natl. Acad. Sci. 103(34): 12763-8. Medline abstract: 16908844
Choi, S. J., et al. (2005). Tsc-22 enhances TGF-beta signaling by associating with Smad4 and induces erythroid cell differentiation, Molec. Cell. Biochem. 271: 23-28. PubMed citation: 15881652
Dobens, L. L., et al. (1997). The Drosophila bunched gene is a homologue of the growth factor stimulated mammalian TSC-22 sequence and is required during oogenesis. Mech. Dev. 65(1-2): 197-208. PubMed citation: 9256356
Dobens, L. L. (2000). Drosophila bunched integrates opposing DPP and EGF signals to set the operculum boundary. Development 127: 745-754. PubMed citation: 10648233
Dobens, L., Jaeger, A., Peterson, J. S. and Raftery, L. A. (2005). Bunched sets a boundary for Notch signaling to pattern anterior eggshell structures during Drosophila oogenesis. Dev. Biol. 287: 425-437. PubMed citation: 16223477
Dohrmann. C. E., et al. (2002). Opposing effects on TSC-22 expression by BMP and receptor tyrosine kinase signals in the developing feather tract. Dev. Dynamics 223: 85-95. PubMed citation: 11803572
Dohrmann, C. E., Belaoussoff, M. and Raftery, L. A. (1999). Dynamic expression of TSC-22 at sites of epithelial-mesenchymal interactions during mouse development. Mech. Dev. 84(1-2): 147-51. PubMed citation: 10473130
Cohen. N., et al. (2006). GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response. Blood 107: 2037-2044. PubMed citation: 16293609
Gupta, R., et al. (2003). Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22. J. Biol. Chem. 278: 7431-7438. PubMed citation; Online text
Hamil, K. G. and Hall, S. H. (1994). Cloning of rat Sertoli cell follicle-stimulating hormone primary response complementary deoxyribonucleic acid: regulation of TSC-22 gene expression. Endocrinology 134(3): 1205-1212. PubMed citation: 8161377
Hashiguchi, A., Okabayashi, K. and Asashima, M. (2004). Role of TSC-22 during early embryogenesis in Xenopus laevis. Dev. Growth Diff. 46: 535-544. PubMed citation: 15610143
Hino, S., et al. (2002). Cytoplasmic TSC-22 (transforming growth factor-beta-stimulated clone-22) markedly enhances the radiation sensitivity of salivary gland cancer cells. BBRC 292: 957-963. PubMed citation: 11944908
Iida, M., et al. (2005). Unique patterns of gene expression changes in liver after treatment of mice for 2 weeks with different known carcinogens and non-carcinogens. Carcinogenesis 26: 689-699. PubMed citation: 15618236
Kawamata, H., et al. (1998). Induction of TSC-22 by treatment with a new anti-cancer drug, vesnarinone, in a human salivary gland cancer cell. Br. J. Cancer 77(1): 71-8. PubMed citation: 9459148
Kester, H. A., Blanchetot, C., den Hertog, J., van der Saag, P. T. and van der Burg, B. (1999). Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity. J Biol Chem 274: 27439-27447. PubMed citation: 10488076
Kolbus, A., et al. (2003). Cooperative signaling between cytokine receptors and the glucocorticoid receptor in the expansion of erythroid progenitors: molecular analysis by expression profiling. Blood 102: 3136-3146. PubMed citation: 12869505
Levine, B., et al. (2007). Notch signaling links interactions between the C/EBP homolog slow border cells and the GILZ homolog bunched during cell migration. Dev. Biol. 305: 217-231. PubMed citation: 17383627
Mittelstadt, P. R. and Ashwell, J. D. (2001). Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ, J. Biol. Chem. 276: 29603-29610. PubMed citation: 11397794
Ohta, S., Shimekake, Y. and Nagata, K. (1996). Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter. Eur. J. Biochem. 242(3): 460-466. PubMed citation: 9022669
Ohta, S., Yanagihara, K. and Nagata, K. (1997). Mechanism of apoptotic cell death of human gastric carcinoma cells mediated by transforming growth factor beta. Biochem. J. 324(3): 777-782. PubMed citation: 9210400
Rentsch, C. A., et al. (2006). Differential expression of TGFbeta-stimulated clone 22 in normal prostate and prostate cancer. Int. J. Cancer 118: 899-906. PubMed citation: 16106424
Riccardi, C., et al. (2001). GILZ, a glucocorticoid hormone induced gene, modulates T lymphocytes activation and death through interaction with NF-kB. Adv. Exp. Med. Biol. 495: 31-39. PubMed citation: 11774584
Seidel, G., Adermann, K., Schindler, T., Ejchart, A., Jaenicke, R., Forssmann, W.-G. and Rosch, P. (1997). Solution structure of porcine delta sleep-inducing peptide immunoreactive peptide A homolog of the shortsighted gene product. J. Biol. Chem. 272: 30918-30927. PubMed citation: 9388238
Shi, X., et al. (2003). A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells. EMBO Rep. 4(4): 374-80. PubMed citation: 12671681
Shibanuma, M., Kuroki, T. and Nose, K. (1992). Isolation of a gene encoding a putative leucine zipper structure that is induced by transforming growth factor beta 1 and other growth factors. J. Biol. Chem. 267(15): 10219-10224. PubMed citation: 1587811
Shostak, K. O., et al. (2003). Downregulation of putative tumor suppressor gene TSC-22 in human brain tumors. J. Surgical Oncol. 82: 57-64. PubMed citation: 12501169
Shostak, K. O., et al. (2005). Patterns of expression of TSC-22 protein in astrocytic gliomas. Exp. Oncology 27: 314-318. PubMed citation: 16404353
Soma, T., et al. (2003). Profile of transforming growth factor-beta responses during the murine hair cycle. J. Inv. Dermatology 121: 969-975. PubMed citation: 14708594
Treisman, J. E., Lai., Z. C., and Rubin. G. M. (1995). Shortsighted acts in the decapentaplegic pathway in Drosophila eye development and has homology to a mouse TGF-beta-responsive gene. Development 121: 2835-2845. PubMed citation: 7555710
Xu, Y., et al. (2003). Primary culture model of peroxisome proliferator-activated receptor gamma activity in prostate cancer cells. J. Cell. Phys. 196: 131-143. PubMed citation: 12767049
Zhang, W., Yang, N. and Shi, X. M. (2008). Regulation of mesenchymal stem cell osteogenic differentiation by glucocorticoid-induced leucine zipper (GILZ). J. Biol. Chem. 283(8): 4723-9. PubMed citation: 18084007
date revised: 30 May 2008
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