Prefoldin 2: Biological Overview | References
Gene name - Prefoldin 2
Cytological map position - 68A4-68A4
Function - chaperone
Symbol - Pfdn2
FlyBase ID: FBgn0010741
Genetic map position - chr3L:11,073,292-11,074,388
NCBI classification - Prefoldin subunit
Cellular location - cytoplasmic
Prefoldin is a molecular chaperone complex that regulates tubulin function in mitosis. This study shows that Prefoldin depletion results in disruption of neuroblast polarity, leading to neuroblast overgrowth in Drosophila larval brains. Interestingly, co-depletion of Prefoldin and Partner of Inscuteable (Pins) leads to the formation of gigantic brains with severe neuroblast overgrowth, despite that Pins depletion alone results in smaller brains with partially disrupted neuroblast polarity. This study shows that Prefoldin acts synergistically with Pins to regulate asymmetric division of both neuroblasts and Intermediate Neural Progenitors (INPs). Surprisingly, co-depletion of Prefoldin and Pins also induces dedifferentiation of INPs back into neuroblasts, while depletion either Prefoldin or Pins alone is insufficient to do so. Furthermore, knocking down either α-tubulin or β-tubulin in pins- mutant background results in INP dedifferentiation back into neuroblasts, leading to the formation of ectopic neuroblasts. Overexpression of α-tubulin suppresses neuroblast overgrowth observed in prefoldin pins double mutant brains. These data elucidate an unexpected function of Prefoldin and Pins in synergistically suppressing dedifferentiation of INPs back into neural stem cells (Zhang, 2016).
Control of tissue homeostasis is a central issue during development. The neural stem cells, or neuroblasts, of the Drosophila larval brain is an excellent model for studying stem cell homeostasis. Asymmetric division of neuroblasts generates a self-renewing neuroblast and a different daughter cell that undergoes differentiation pathway to produce neurons or glia. Following each asymmetric division, apical proteins such as aPKC are segregated into the neuroblast daughter and function as 'proliferation factor', while basal proteins are segregated into a smaller daughter cell to act as 'differentiation factors'. At the onset of mitosis, the Partitioning defective (Par) protein complex that is composed of Bazooka (Baz)/Par3, Par6 and atypical protein kinase C (aPKC) is asymmetrically localized at the apical cortex of the neuroblast. Other apical proteins including Partner of Inscuteable (Pins), the heterotrimeric G protein Gαi, and Mushroom body defect (Mud) also accumulate at the apical cortex through an interaction of Inscuteable (Insc) with Par protein complex. Apical proteins control basal localization of cell fate determinants Numb, Prospero (Pros), Brain tumor (Brat) and their adaptor proteins Miranda (Mira) and Partner of Numb (Pon) that are segregated into the ganglion mother cell (GMC) following divisions. Apical proteins and their regulators also control mitotic spindle orientation to ensure correct asymmetric protein segregation at telophase. Several centrosomal proteins, Aurora A, Polo and Centrosomin, regulate mitotic spindle orientation (Zhang, 2016).
There are at least two different types of neuroblasts that undergo asymmetric division in the larval central brain. Perturbation of asymmetric division in either type of neuroblast can trigger neuroblast overproliferation and/or the induction of brain tumors. The majority of neuroblasts are type I neuroblasts that generate a neuroblast and a GMC in each division, while type II neuroblasts generate a neuroblast and an intermediate neural progenitor (INP), which undergoes three to five rounds of asymmetric division to produce GMCs. Ets transcription factor Pointed (PntP1 isoform), exclusively expressed in type II neuroblast lineages, promotes the formation of INPs. Failure to restrict the self-renewal potential of INPs can lead to dedifferentiation, allowing INPs to revert back into 'ectopic neuroblasts'. Notch antagonist Numb and Brat function cooperatively to promote the INP fate. Loss of brat or numb leads to 'ectopic type II neuroblasts' originating from uncommitted immature INPs that failed to undergo maturation. A zinc-finger transcription factor Earmuff functions after Brat and Numb in immature INPs to prevent their dedifferentiation. Earmuff also associates with Brahma and HDAC3, which are involved in chromatin remodeling, to prevent INP dedifferentiation. However, the underlying mechanism by which INPs possess limited developmental potential is largely unknown (Zhang, 2016).
Prefoldin (Pfdn) was first identified as a hetero-hexameric chaperone consisting of two α-like (PFDN3 and 5) and four β-like (PFDN 1, 2, 4 and 6) subunits, based on its ability to capture unfolded actin (Vainberg, 1998). Prefoldin promotes folding of proteins such as tubulin and actin by binding specifically to cytosolic chaperonin containing TCP-1 (CCT) and by directing target proteins to it (Vainberg, 1998). The yeast homologs of Prefoldin 2–6, named GIM1-5 (genes involved in microtubule biogenesis) are present in a complex that facilitates proper folding of α-tubulin and γ-tubulin (Geissler, 1998). All Prefoldin subunits are phylogenetically conserved from Archaea to Eukarya. Structural study of the Prefoldin hexamer from the archaeum M. thermoautotrophicum showed that Prefoldin forms a jellyfish-like shape consisting of a double β barrel assembly with six long tentacle-like coiled coils that participate in substrate binding (Siegert, 2000). The function of Prefoldin as a chaperone has also been illustrated in lower eukaryotes like C. elegans, in which loss of prefoldin resulted in defects in cell division due to reduced microtubule growth rate (Lundin, 2008). Depletion of PFDN1 in mice displayed cytoskeleton-related defects, including neuronal loss and lymphocyte development defects (Cao, 2008). The only Prefoldin subunit in Drosophila that has been characterized to date, Merry-go-round (Mgr), the Pfdn3 subunit, cooperates with the tumor suppressor Von Hippel Lindau (VHL) to regulate tubulin stability (Delgehyr, 2012). However, the functions of Prefoldin in the nervous system remain elusive (Zhang, 2016).
This study describes the critical role of evolutionarily-conserved Prefoldin complex in regulating neuroblast and INP asymmetric division and suppressing INP dedifferentiation. Mutants for two Prefoldin subunits, Mgr and Pfdn2, displayed neuroblast overgrowth with defects in cortical polarity of Par proteins and microtubule-related abnormalities. Interestingly, co-depletion of Pins in mgr or pfdn2 mutants led to massive neuroblast overgrowth. Prefoldin and Pins synergistically regulate asymmetric division of both neuroblasts and INPs. Surprisingly, they also synergistically suppress dedifferentiation of INPs back into neuroblasts. Knocking down tubulins in pins mutant background resulted in severe neuroblasts overgrowth, mimicking that caused by co-depletion of Prefoldin and Pins. These data provide a new mechanism by which Prefoldin and Pins regulates neural stem cell homeostasis through regulating tubulin stability in both neuroblasts and INPs (Zhang, 2016).
pfdn2/CG6302, encoding a Prefoldin β-like subunit, was identified from a RNA interference (RNAi) screen in larval brains. Ectopic neuroblasts labeled by a neuroblast marker, Deadpan (Dpn), were formed upon knocking down pfdn2 under a neuroblast driver insc-Gal4. Only one neuroblast was observed in control type I neuroblast lineages using insc-Gal4 and type II neuroblast lineages using worniu-Gal4 with asense (ase)-Gal80. In contrast, upon pfdn2 RNAi excess neuroblasts were observed in both type I neuroblast lineages and type II neuroblast lineages, respectively. To verify the function of Pfdn2 in neuroblasts, a putative hypomorphic allele of pfdn2, pfdn201239, was analyzed that has a P element inserted at the 5′ untranslated region (UTR) of pfdn2. Hemizygous larval brains of pfdn201239 over Df(3L)BSC457 (referred to as pfdn2− thereafter) displayed 235.3 ± 31.7 neuroblasts per brain hemisphere, suggesting that Pfdn2 inhibits the formation of ectopic neuroblasts in larval brains. Consistently, an increase of EdU (5-ethynyl-2′-deoxyuridine)-incorporation was also observed in pfdn2− mutants compared to the control. To generate pfdn2 null alleles, a P element, EY06124, was mobilized. Its imprecise excision yielded two loss-of-function alleles, pfdn2Δ10 and pfdn2Δ17, both deleting the entire opening reading frame (ORF) of pfdn2. pfdn2Δ10 and pfdn2Δ17 mutants survive to pupal stage and display strong phenotypes with ectopic neuroblasts labeled by Dpn. These phenotypes in pfdn2Δ10 and pfdn2Δ17 mutant brains can be fully rescued by overexpression of wild-type pfdn2 or pfdn2-Venus transgene. Pfdn2 is abundantly expressed in neuroblasts, INPs and their immediate neural progeny- GMCs, detected by a specific antibody generated against Pfdn2 full length and a transgenic Pfdn2 with a Venus tag at the C-terminus. In addition, Pfdn2 expression under the tubulin-Gal4 fully rescued the lethality of both pfdn2Δ10 and pfdn2Δ17 mutants. Pfdn2 protein was undetectable in pfdn2Δ10 zygotic mutants, further supporting that it is a null allele. Both type I and type II MARCM (Mosaic Analysis with Repressible Cell Marker) clones of pfdn2Δ10 generated excess neuroblasts. These phenotypes were slightly weaker than pfdn2Δ10 zygotic mutants, likely due to residual Pfdn2 protein in the clones. These data indicate that Pfdn2 is required in both type I and type II neuroblast lineages to prevent the formation of ectopic neuroblasts (Zhang, 2016).
This study has identified an unexpected synergism between Prefoldin and Pins in suppressing neuroblasts overgrowth. Barious subunits of Prefoldin complex are implicated in asymmetric division of neuroblasts, especially during asymmetric protein segregation at telophase. It is known that depletion of Pins results in the formation of smaller larval brains, despite partial loss of neuroblasts polarity. Interestingly, co-depletion of Pfdn2 and Pins results in severe neuroblasts overgrowth, while Pfdn2 depletion alone only causes mild brain overgrowth. This phenotype is contributed by a combination of loss of neuroblast polarity, defects of asymmetric division of INPs, as well as INP dedifferentiation. Knocking down tubulins in pins mutant background mimics the co-depletion of Prefoldin and Pins, suggesting that tubulin stability appears to be critical for the suppression of neuroblast overgrowth in the absence of Pins function. The data also suggest that Prefoldin function and tubulin stability in INPs are important to suppress their dedifferentiation back into neuroblasts (Zhang, 2016).
How microtubules induce cortical polarity is poorly understood in Drosophila neuroblasts. Previously, one report showed that kinesin Khc-73, which localized at the plus end of astral microtubules, and Discs large (Dlg) induced cortical polarization of Pins/Gαi in neuroblasts (Siegrist, 2005). However, microtubules are considered not essential for neuroblast polarity. This study shows that Drosophila Prefoldin regulates asymmetric division of both neuroblasts and INPs through tubulins, suggesting an important role of microtubules in neuroblast polarity. The essential role of microtubules directly regulating cell polarity is found in various systems. During C. elegans meiosis, a microtubule-organizing center is necessary and sufficient for the establishment of the anterior-posterior polarity. In the fission yeast Schizosaccharomyces pombe, interphase microtubules directly regulate cell polarity through proteins such as tea1p. In mammalian airway cilia, microtubules are required for asymmetric localization of planer cell polarity proteins (Zhang, 2016).
This study shows that the role of Drosophila Prefoldin complex in regulating asymmetric division is very likely dependent on microtubules. This is consistent with the known essential role of Prefoldin for maintaining tubulin levels in various organisms such as yeast, C. elegans, plants and mammals. In yeast, Gim (Prefoldin) null mutants become super-sensitive to the microtubule-depolymerizing drug benomyl as a result of a reduced level of α-tubulin. In the absence of Prefoldin, the function of the chaperone pathway is damaged and unable to fold sufficient amount of tubulins for normal yeast growth. In C. elegans, reducing Prefoldin function causes defects in cell division presumably due to the reduction of tubulin levels and microtubule growth rate (Lundin, 2008). Genetic analysis of mammalian Prefoldin also suggests that cytoskeletal proteins like actin and tubulin make up the major substrate of Prefoldin in mammals (Cao, 2008). These studies in different organisms together suggest that Prefoldin complex plays a conserved central role in tubulin folding (Zhang, 2016).
'Telophase rescue', a term refers to the phenomenon that protein mis-localization at metaphase is completely restored at telophase, is observed in many mutants that affect neuroblast asymmetric division. However, both apical and basal proteins are still mis-segregated in pfdn2 and mgr mutants, suggesting that 'telophase rescue' is defective in these mutants. Telophase rescue is regulated by TNF receptor-associated factor (DTRAF1), which binds to Baz and acts downstream of Egr/TNF (Wang, 2006). Telophase rescue also depends on Worniu/Escargot/Snail family proteins and a microtubule-dependent Khc-73/Dlg pathway. Pins did not form a protein complex with Mgr, α-tubulin or β-tubulin in co-immunoprecipitation assay. Given that Dlg is a Pins-interacting protein, Prefoldin appears to function in a different pathway with Dlg or Khc-73 during asymmetric division (Zhang, 2016).
Recently, merry-go-round (mgr), encoding Prefoldin 3 (Pfdn3)/VBP1/Gim2 subunit, was reported to regulate spindle assembly (Delgehyr, 2012). Loss of mgr led to formation of monopolar mitotic spindles and loss of centrosomes because of improper folding and destabilization of tubulins. The current analysis on Pfdn2 indicates that pfdn2 mutants displayed similar spindle and centrosome abnormalities. In addition, the incorrectly folded tubulin due to loss of mgr may be eliminated by Drosophila von Hippel Lindau protein (Vhl), an E3 ubiquitin-protein ligase. Interestingly, the data suggest that Prefoldin has a tumor-suppressor like function in preventing neuroblast overgrowth. However, Drosophila Vhl is not important for brain tumor suppression, as its loss-of-function neither affects number of neuroblasts nor suppresses overgrowth observed in pfdn2 RNAi or mgr RNAi (Zhang, 2016).
This study shows a novel synergism between Prefoldin and Pins in suppressing dedifferentiation of INPs back into neuroblasts. Prefoldin and Pins apparently suppress dedifferentiation through regulating tubulin levels. It is likely that appropriate tubulin levels in INPs are important for their differentiation, while reducing tubulin levels can increase the risk of INP dedifferentiation. Currently, several cell fate determinants such as Brat, Numb and the SWI/SNF chromatin remodeling complex with its cofactors Erm and Hdac3 are critical to suppress INP dedifferentiation back into neuroblast. It is currently unknown whether or how Prefoldin/Pins are linked to these known suppressors of dedifferentiation. It is possible that symmetric division of INPs causes reduced levels of Brat and Numb in these abnormal INP daughters, leading to their dedifferentiation. Alternatively, Prefoldin might regulate transcription of genes within INPs to suppress dedifferentiation. It was reported that the human homolog of Pfdn5, MM-1, has a role in transcriptional regulation by binding to the E-box domain of c-Myc and represses E-box-dependent transcriptional activity. Interestingly, Prefoldin Subunit 5 gene is deleted in Canine mammary tumors, suggesting that it may be a tumor suppressor gene. This study has revealed a novel mechanism by which Prefoldin and Pins function through tubulin stability to suppress stem cell overgrowth. It is expected to contribute to the understanding of mammalian/human Prefoldin function in tumorigenesis (Zhang, 2016).
Mutations in Drosophila merry-go-round (mgr) have been known for over two decades to lead to circular mitotic figures and loss of meiotic spindle integrity. However, the identity of its gene product has remained undiscovered. Thus study shows that mgr encodes the Prefoldin subunit counterpart of human von Hippel Lindau binding-protein 1. Depletion of Mgr from cultured cells also leads to formation of monopolar and abnormal spindles and centrosome loss. These phenotypes are associated with reductions of tubulin levels in both mgr flies and mgr RNAi-treated cultured cells. Moreover, mgr spindle defects can be phenocopied by depleting beta-tubulin, suggesting Mgr function is required for tubulin stability. Instability of beta-tubulin in the mgr larval brain is less pronounced than in either mgr testes or in cultured cells. However, expression of transgenic beta-tubulin in the larval brain leads to increased tubulin instability, indicating that Prefoldin might only be required when tubulins are synthesized at high levels. Mgr interacts with Drosophila von Hippel Lindau protein (Vhl). Both proteins interact with unpolymerized tubulins, suggesting they cooperate in regulating tubulin functions. Accordingly, codepletion of Vhl with Mgr gives partial rescue of tubulin instability, monopolar spindle formation, and loss of centrosomes, leading to a proposal of a requirement for Vhl to promote degradation of incorrectly folded tubulin in the absence of functional Prefoldin. Thus, Vhl may play a pivotal role: promoting microtubule stabilization when tubulins are correctly folded by Prefoldin and tubulin destruction when they are not (Delgehyr, 2012).
The finding that the Drosophila merry-go-round gene encodes a subunit of the Prefoldin complex has allowed the accounting for aberrant structure and function of spindles and centrosomes in cells depleted of its gene product. The inability to correctly fold tubulins in Prefoldin-deficient cells leads to tubulin instability and, hence, defects that can be phenocopied by depleting β- or γ-tubulin. However, whereas β-tubulin depletion phenocopied all of the defects observed, γ-tubulin depletion only recapitulated some of them. The more dramatic phenotypes seen in Mgr-deficient cells expressing high levels of tubulin (primary spermatocytes and neuroblasts expressing a β-tubulin transgene) suggest that the Prefoldin complex is critical to maintain tubulin levels above a certain threshold of tubulin expression. This finding could be a consequence of the impact of an excess of tubulin upon its complex folding pathway. Interestingly, in mammalian cells, increased soluble tubulin, in response to a MT-destabilizing agent, leads to the rapid degradation of tubuline. In Drosophila, tubulins in the testes are the most affected by the absence of Mgr compared with other tissues. Indeed, it may be of particular importance to regulate tubulin levels at the late stages of spermatogenesis, where the very large meiotic cells are provided with proportionally large amounts of tubulin that are used in the meiotic spindle but have a major additional purpose: the building of the sperm tail. Similarly, in the mouse, the effects of depletion or mutation of prefoldin subunits are largely restricted to the brain, where tubulin levels are also very high. Whether this tissue specificity is a consequence of tubulin levels will be an interesting question to address. Finally, the demonstration that Vhl is required for tubulin destruction in the absence of Mgr and the ability of Vhl to interact with tubulin monomers and dimers raises the possibility that its role as an E3 ubiquitin-protein ligase could come to play in regulating tubulin levels (Delgehyr, 2012).
The idea that Vhl and Prefoldin can cooperate in regulating protein stability was also raised by Mousnier (2007), who identified the prefoldin subunit VBP1 as a binding partner of the HIV-1 viral integrase and suggested this mediated the interaction of the integrase with the Cul2-Vhl E3-Ubiquitin ligase. This finding led these authors to suggest a role for prefoldin at a pivotal part of the pathway that would determine whether a protein was passed on to the CCT chaperonin for folding or to the proteasome for degradation. Similarly, it can be speculated that prefoldin as a partner of Vhl may well serve a key role in regulating the equilibrium between tubulin targeted for destruction or for folding and incorporation into MTs. The concentration of assembly-competent tubulin must be tightly controlled because it affects cytoskeletal dynamics. Vhl might contribute to this influence by an effect on MT dynamics through interaction with MAPs on the MT lattice and by intervening in the regulation of tubulin folding. There is growing evidence for a critical function of Vhl in stabilizing cytoplasmic MTs and axonemal MTs in response to levels of soluble tubulin. Reciprocally, MT stability can contribute to regulating levels of proteins that are targets of the Cul2-Vhl E3-Ubiquitin ligase, such as the HIF proteins, the levels of which fall when their mRNAs accumulate in cytoplasmic P-bodies for translational repression following MT disruption. It will be important in future to consider the roles played by the Prefoldin complex and Vhl to understand the interrelationships between the machinery regulating tubulin levels in relation to MT stability, both in normal and tumor cells (Delgehyr, 2012).
Misfolded proteins challenge the ability of cells to maintain protein homeostasis and can accumulate into toxic protein aggregates. As a consequence, cells have adopted a number of protein quality control pathways to prevent protein aggregation, promote protein folding, and target terminally misfolded proteins for degradation. This study employed a thermosensitive allele of the yeast Guk1 guanylate kinase as a model misfolded protein to investigate degradative protein quality control pathways. A flow cytometry based screen was performed to identify factors that promote proteasomal degradation of proteins misfolded as the result of missense mutations. In addition to the E3 ubiquitin ligase Ubr1, the prefoldin chaperone subunit Gim3 was identified as an important quality control factor. Whereas the absence of GIM3 did not impair proteasomal function or the ubiquitination of the model substrate, it led to the accumulation of the poorly soluble model substrate in cellular inclusions that was accompanied by delayed degradation. Gim3 interacted with the Guk1 mutant allele, and it is proposed that prefoldin promotes the degradation of the unstable model substrate by maintaining the solubility of the misfolded protein. It was also demonstrated that in addition to the Guk1 mutant, prefoldin can stabilize other misfolded cytosolic proteins containing missense mutations (Comyn, 2016).
Transcriptional elongation requires the concerted action of several factors that allow RNA polymerase II to advance through chromatin in a highly processive manner. In order to identify novel elongation factors, z systematic yeast genetic screening was performed based on the GLAM (Gene Length-dependent Accumulation of mRNA) assay, which is used to detect defects in the expression of long transcription units. Apart from well-known transcription elongation factors, mutants were identified in the prefoldin complex subunits, which were among those that caused the most dramatic phenotype. Prefoldin, so far involved in the cytoplasmic co-translational assembly of protein complexes, is also present in the nucleus, and a subset of its subunits are recruited to chromatin in a transcription-dependent manner. Prefoldin influences RNA polymerase II elongation rate in vivo and plays an especially important role in the transcription elongation of long genes and those whose promoter regions contain a canonical TATA box. Finally, a specific functional link was found between prefoldin and histone dynamics after nucleosome remodeling, which is consistent with the extensive network of genetic interactions between this factor and the machinery regulating chromatin function. This study establishes the involvement of prefoldin in transcription elongation, and supports a role for this complex in cotranscriptional histone eviction (Millan-Zambrano, 2013).
Search PubMed for articles about Drosophila Prefoldin
Cao, S., Carlesso, G., Osipovich, A. B., Llanes, J., Lin, Q., Hoek, K. L., Khan, W. N. and Ruley, H. E. (2008). Subunit 1 of the prefoldin chaperone complex is required for lymphocyte development and function. J Immunol 181(1): 476-484. PubMed ID: 18566413.
Comyn, S. A., Young, B. P., Loewen, C. J. and Mayor, T. (2016). Prefoldin promotes proteasomal degradation of cytosolic proteins with missense mutations by maintaining substrate solubility. PLoS Genet 12(7): e1006184. PubMed ID: 27448207
Delgehyr, N., Wieland, U., Rangone, H., Pinson, X., Mao, G., Dzhindzhev, N. S., McLean, D., Riparbelli, M. G., Llamazares, S., Callaini, G., Gonzalez, C. and Glover, D. M. (2012). Drosophila Mgr, a Prefoldin subunit cooperating with von Hippel Lindau to regulate tubulin stability. Proc Natl Acad Sci U S A 109(15): 5729-5734. PubMed ID: 22451918
Geissler, S., Siegers, K. and Schiebel, E. (1998). A novel protein complex promoting formation of functional alpha- and gamma-tubulin. EMBO J 17(4): 952-966. PubMed ID: 9463374
Lundin, V. F., Srayko, M., Hyman, A. A. and Leroux, M. R. (2008). Efficient chaperone-mediated tubulin biogenesis is essential for cell division and cell migration in C. elegans. Dev Biol 313(1): 320-334. PubMed ID: 18062952
Millan-Zambrano, G., Rodriguez-Gil, A., Penate, X., de Miguel-Jimenez, L., Morillo-Huesca, M., Krogan, N. and Chavez, S. (2013). The prefoldin complex regulates chromatin dynamics during transcription elongation. PLoS Genet 9(9): e1003776. PubMed ID: 24068951
Mousnier, A., Kubat, N., Massias-Simon, A., Segeral, E., Rain, J. C., Benarous, R., Emiliani, S. and Dargemont, C. (2007). von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step. Proc Natl Acad Sci U S A 104(34): 13615-13620. PubMed ID: 17698809
Siegert, R., Leroux, M. R., Scheufler, C., Hartl, F. U. and Moarefi, I. (2000). Structure of the molecular chaperone prefoldin: unique interaction of multiple coiled coil tentacles with unfolded proteins. Cell 103(4): 621-632. PubMed ID: 11106732
Siegrist, S. E. and Doe, C. Q. (2005). Microtubule-induced Pins/Galphai cortical polarity in Drosophila neuroblasts. Cell 123(7): 1323-1335. PubMed ID: 16377571
Vainberg, I. E., Lewis, S. A., Rommelaere, H., Ampe, C., Vandekerckhove, J., Klein, H. L. and Cowan, N. J. (1998). Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell 93(5): 863-873. PubMed ID: 9630229
Wang, H., Cai, Y., Chia, W. and Yang, X. (2006). Drosophila homologs of mammalian TNF/TNFR-related molecules regulate segregation of Miranda/Prospero in neuroblasts. EMBO J 25(24): 5783-5793. PubMed ID: 17139248
Zhang, Y., Rai, M., Wang, C., Gonzalez, C. and Wang, H. (2016). Prefoldin and Pins synergistically regulate asymmetric division and suppress dedifferentiation. Sci Rep 6: 23735. PubMed ID: 27025979
date revised: 22 July 2017
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