Gene Symbol: RPN4
Description: stress-regulated transcription factor RPN4
Alias: SON1, UFD5, stress-regulated transcription factor RPN4
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Hahn J, Neef D, Thiele D. A stress regulatory network for co-ordinated activation of proteasome expression mediated by yeast heat shock transcription factor. Mol Microbiol. 2006;60:240-51 pubmed
    ..One such target, the RPN4 gene, encodes a transcription factor that directly activates expression of a number of genes encoding proteasome ..
  2. Mannhaupt G, Schnall R, Karpov V, Vetter I, Feldmann H. Rpn4p acts as a transcription factor by binding to PACE, a nonamer box found upstream of 26S proteasomal and other genes in yeast. FEBS Lett. 1999;450:27-34 pubmed
    ..Additionally, we found the proteasome-associated control element to occur in a number of promoters to genes which are related to the ubiquitin-proteasome pathway in yeast. ..
  3. Park S, Roelofs J, Kim W, Robert J, Schmidt M, Gygi S, et al. Hexameric assembly of the proteasomal ATPases is templated through their C termini. Nature. 2009;459:866-70 pubmed publisher
    ..Our studies show that assembly of the proteasome base is a rapid yet highly orchestrated process. ..
  4. Wang X, Xu H, Ha S, Ju D, Xie Y. Proteasomal degradation of Rpn4 in Saccharomyces cerevisiae is critical for cell viability under stressed conditions. Genetics. 2010;184:335-42 pubmed publisher
    ..homeostasis in Saccharomyces cerevisiae is regulated by a negative feedback loop in which the transcription factor Rpn4 induces the proteasome genes and is rapidly degraded by the assembled proteasome...
  5. London M, Keck B, Ramos P, Dohmen R. Regulatory mechanisms controlling biogenesis of ubiquitin and the proteasome. FEBS Lett. 2004;567:259-64 pubmed
    ..In these mutants, transcriptional induction of UBI4 was depending in part on the transcription factor Rpn4. Deletion of UBI4 partially suppressed the growth defects of ump1 mutants, indicating that accumulation of ..
  6. Haugen A, Kelley R, Collins J, Tucker C, Deng C, Afshari C, et al. Integrating phenotypic and expression profiles to map arsenic-response networks. Genome Biol. 2004;5:R95 pubmed
    ..profiling of specific deletion strains, confirming that the transcription factors Yap1, Arr1 (Yap8), and Rpn4 strongly mediate the cell's adaptation to arsenic-induced stress but that Cad1 has negligible impact...
  7. Salin H, Fardeau V, Piccini E, Lelandais G, Tanty V, Lemoine S, et al. Structure and properties of transcriptional networks driving selenite stress response in yeasts. BMC Genomics. 2008;9:333 pubmed publisher
  8. Ju D, Wang X, Xu H, Xie Y. Genome-wide analysis identifies MYND-domain protein Mub1 as an essential factor for Rpn4 ubiquitylation. Mol Cell Biol. 2008;28:1404-12 pubmed
    The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative feedback circuit in which the Rpn4 transcription factor upregulates the proteasome genes and is rapidly degraded by the proteasome...
  9. Ju D, Xu H, Wang X, Xie Y. Ubiquitin-mediated degradation of Rpn4 is controlled by a phosphorylation-dependent ubiquitylation signal. Biochim Biophys Acta. 2007;1773:1672-80 pubmed
    ..Our previous work has mapped the ubiquitylation signal of Rpn4, the transcription activator for the Saccharomyces cerevisiae proteasome genes, to an N-terminal acidic domain (NAD)..

More Information


  1. Ju D, Xie Y. Identification of the preferential ubiquitination site and ubiquitin-dependent degradation signal of Rpn4. J Biol Chem. 2006;281:10657-62 pubmed
    ..Here we studied the mechanism underlying ubiquitin-dependent degradation of Rpn4, a transcription activator of the Saccharomyces cerevisiae proteasome genes...
  2. Ju D, Wang L, Mao X, Xie Y. Homeostatic regulation of the proteasome via an Rpn4-dependent feedback circuit. Biochem Biophys Res Commun. 2004;321:51-7 pubmed
    ..Early studies showed that Rpn4 (also named Son1 and Ufd5) is a transcriptional activator of the Saccharomyces cerevisiae proteasome genes, and that Rpn4 is rapidly degraded ..
  3. Wang L, Mao X, Ju D, Xie Y. Rpn4 is a physiological substrate of the Ubr2 ubiquitin ligase. J Biol Chem. 2004;279:55218-23 pubmed
    ..the proteasome in Saccharomyces cerevisiae is controlled by a feedback circuit in which transcriptional activator Rpn4 up-regulates the proteasome genes and is destroyed by the assembled, active proteasome...
  4. Le Tallec B, Barrault M, Guerois R, Carré T, Peyroche A. Hsm3/S5b participates in the assembly pathway of the 19S regulatory particle of the proteasome. Mol Cell. 2009;33:389-99 pubmed publisher
    ..Finally, we identify the putative species-specific 19S subunit S5b as a functional homolog of the Hsm3 chaperone in mammals. These findings shed light on chaperone-assisted proteasome assembly in eukaryotes. ..
  5. Jelinsky S, Estep P, Church G, Samson L. Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with proteasomes. Mol Cell Biol. 2000;20:8157-67 pubmed
    ..Moreover, transcription of these genes is modulated by the proteasome-associated protein Rpn4, most likely via its binding to MAG1 upstream repressor sequence 2-like elements, that turn out to be almost ..
  6. Hausmann S, Zheng S, Costanzo M, Brost R, Garcin D, Boone C, et al. Genetic and biochemical analysis of yeast and human cap trimethylguanosine synthase: functional overlap of 2,2,7-trimethylguanosine caps, small nuclear ribonucleoprotein components, pre-mRNA splicing factors, and RNA decay pathways. J Biol Chem. 2008;283:31706-18 pubmed publisher
    ..implicated in RNA end processing and decay (Pat1, Lsm1, and Trf4) and regulation of polymerase II transcription (Rpn4, Spt3, Srb2, Soh1, Swr1, and Htz1)...
  7. Fujimuro M, Tanaka K, Yokosawa H, Toh e A. Son1p is a component of the 26S proteasome of the yeast Saccharomyces cerevisiae. FEBS Lett. 1998;423:149-54 pubmed
    A son1 mutant was isolated as a mutant showing synthetic lethality with nin1-1 which is defective in the p31 component of the regulatory subunit of the yeast 26S proteasome...
  8. Xie Y, Varshavsky A. RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: a negative feedback circuit. Proc Natl Acad Sci U S A. 2001;98:3056-61 pubmed
    The RPN4 (SON1, UFD5) protein of the yeast Saccharomyces cerevisiae is required for normal levels of intracellular proteolysis. RPN4 is a transcriptional activator of genes encoding proteasomal subunits...
  9. Wang X, Xu H, Ju D, Xie Y. Disruption of Rpn4-induced proteasome expression in Saccharomyces cerevisiae reduces cell viability under stressed conditions. Genetics. 2008;180:1945-53 pubmed publisher
    ..in Saccharomyces cerevisiae is regulated by a negative feedback circuit in which the transcription activator Rpn4 upregulates the proteasome genes and is rapidly degraded by the assembled proteasome...
  10. Teixeira M, Dias P, Simões T, Sá Correia I. Yeast adaptation to mancozeb involves the up-regulation of FLR1 under the coordinate control of Yap1, Rpn4, Pdr3, and Yrr1. Biochem Biophys Res Commun. 2008;367:249-55 pubmed
  11. Nelson M, Kurihara T, Silver P. Extragenic suppressors of mutations in the cytoplasmic C terminus of SEC63 define five genes in Saccharomyces cerevisiae. Genetics. 1993;134:159-73 pubmed
    ..Five complementation groups of extragenic mutations, son1-son5 (suppressor of npl1-1), were identified among the recessive suppressors...
  12. Xu B, Kurjan J. Evidence that mating by the Saccharomyces cerevisiae gpa1Val50 mutant occurs through the default mating pathway and a suggestion of a role for ubiquitin-mediated proteolysis. Mol Biol Cell. 1997;8:1649-64 pubmed
    ..Two suppressor genes corresponded to SON1/UFD5 and SEN3, which are implicated in ubiquitin-mediated proteolysis...
  13. Ha S, Ju D, Xie Y. The N-terminal domain of Rpn4 serves as a portable ubiquitin-independent degron and is recognized by specific 19S RP subunits. Biochem Biophys Res Commun. 2012;419:226-31 pubmed publisher
    ..Here we demonstrated that the Ub-independent degradation of Rpn4 requires the 19S regulatory particle (RP)...
  14. Chien C, Chen R. Cdc48 chaperone and adaptor Ubx4 distribute the proteasome in the nucleus for anaphase proteolysis. J Biol Chem. 2013;288:37180-91 pubmed publisher
    ..Moreover, genetic analysis reveals that ubx4 deletion mutant dies in the absence of Rpn4, a transcriptional activator for proteasome subunits, and the proteasome chaperone Ump1, indicating that an optimal ..
  15. Marshall R, McLoughlin F, Vierstra R. Autophagic Turnover of Inactive 26S Proteasomes in Yeast Is Directed by the Ubiquitin Receptor Cue5 and the Hsp42 Chaperone. Cell Rep. 2016;16:1717-1732 pubmed publisher
    ..Together, Cue5 and Hsp42 provide a quality control checkpoint in yeast directed at recycling dysfunctional 26S proteasomes. ..
  16. Hitchcock A, Krebber H, Frietze S, Lin A, Latterich M, Silver P. The conserved npl4 protein complex mediates proteasome-dependent membrane-bound transcription factor activation. Mol Biol Cell. 2001;12:3226-41 pubmed
    ..Given the recent finding that NPL4 is allelic to the ERAD gene HRD4, we further propose that this NPL4 function extends to all endoplasmic reticulum-membrane-associated targets of the proteasome. ..
  17. Yashiroda H, Mizushima T, Okamoto K, Kameyama T, Hayashi H, Kishimoto T, et al. Crystal structure of a chaperone complex that contributes to the assembly of yeast 20S proteasomes. Nat Struct Mol Biol. 2008;15:228-36 pubmed publisher
    ..The structure of the Dmp1-Dmp2-alpha5 complex reveals how this chaperone functions in proteasome assembly and why it dissociates from proteasome precursors before the beta-rings are assembled. ..
  18. Yeh C, Chang S, Chen J, Wang H, Chou Y, Wang C, et al. The conserved AU dinucleotide at the 5' end of nascent U1 snRNA is optimized for the interaction with nuclear cap-binding-complex. Nucleic Acids Res. 2017;45:9679-9693 pubmed publisher
    ..Our data also provide a structural interpretation as to why the AU dinucleotide is conserved during evolution. ..
  19. Le Tallec B, Barrault M, Courbeyrette R, Guerois R, Marsolier Kergoat M, Peyroche A. 20S proteasome assembly is orchestrated by two distinct pairs of chaperones in yeast and in mammals. Mol Cell. 2007;27:660-74 pubmed
    ..Our findings provide evidence for a remarkable conservation of a pairwise chaperone-assisted proteasome assembly throughout evolution. ..
  20. Laribee R, Shibata Y, Mersman D, Collins S, Kemmeren P, Roguev A, et al. CCR4/NOT complex associates with the proteasome and regulates histone methylation. Proc Natl Acad Sci U S A. 2007;104:5836-41 pubmed
    ..These studies implicate CCR4/NOT in the regulation of H3K4me3 through a ubiquitin-dependent pathway that likely involves the proteasome. ..
  21. Crosas B, Hanna J, Kirkpatrick D, Zhang D, Tone Y, Hathaway N, et al. Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities. Cell. 2006;127:1401-13 pubmed
    ..We propose that through dynamic remodeling of ubiquitin chains, proteasomes actively regulate substrate commitment to degradation. ..
  22. Stadtmueller B, Kish Trier E, Ferrell K, Petersen C, Robinson H, Myszka D, et al. Structure of a proteasome Pba1-Pba2 complex: implications for proteasome assembly, activation, and biological function. J Biol Chem. 2012;287:37371-82 pubmed publisher
    ..These findings extend understanding of proteasome interactions with HbYX motifs and suggest multiple roles for Pba1-Pba2 interactions throughout proteasome assembly and function. ..
  23. Fleming J, Lightcap E, Sadis S, Thoroddsen V, Bulawa C, Blackman R. Complementary whole-genome technologies reveal the cellular response to proteasome inhibition by PS-341. Proc Natl Acad Sci U S A. 2002;99:1461-6 pubmed
    ..Used together, these complementary technologies provide a general and powerful means to elucidate the cellular ramifications of drug treatment. ..
  24. Curwin A, LeBlanc M, Fairn G, McMaster C. Localization of lipid raft proteins to the plasma membrane is a major function of the phospholipid transfer protein Sec14. PLoS ONE. 2013;8:e55388 pubmed publisher
    ..Localization of both lipid raft proteins was restored upon increased expression of the sec14(ts) allele. We suggest that a major function provided by Sec14 is trafficking and localization of lipid raft proteins. ..
  25. Dange T, Smith D, Noy T, Rommel P, Jurzitza L, Cordero R, et al. Blm10 protein promotes proteasomal substrate turnover by an active gating mechanism. J Biol Chem. 2011;286:42830-9 pubmed publisher
  26. Batenchuk C, Tepliakova L, Kaern M. Identification of response-modulated genetic interactions by sensitivity-based epistatic analysis. BMC Genomics. 2010;11:493 pubmed publisher
    ..While the method was developed for growth phenotype, it should apply equally well for other phenotypes, including the expression of fluorescent reporters. ..
  27. Ju D, Wang X, Ha S, Fu J, Xie Y. Inhibition of proteasomal degradation of rpn4 impairs nonhomologous end-joining repair of DNA double-strand breaks. PLoS ONE. 2010;5:e9877 pubmed publisher
    ..in Saccharomyces cerevisiae is regulated by a negative feedback circuit in which the transcription factor Rpn4 induces the proteasome genes and is rapidly degraded by the assembled proteasome...
  28. Ju D, Xu H, Wang X, Xie Y. The transcription activation domain of Rpn4 is separate from its degrons. Int J Biochem Cell Biol. 2010;42:282-6 pubmed publisher
    ..in Saccharomyces cerevisiae is regulated by a negative feedback circuit in which the transcription activator Rpn4 upregulates the proteasome genes and is rapidly degraded by the assembled proteasome...
  29. Laribee R, Krogan N, Xiao T, Shibata Y, Hughes T, Greenblatt J, et al. BUR kinase selectively regulates H3 K4 trimethylation and H2B ubiquitylation through recruitment of the PAF elongation complex. Curr Biol. 2005;15:1487-93 pubmed
    ..Our data reveal a novel function for the BUR kinase in transcriptional regulation through the selective control of histone modifications. ..
  30. Karpov D, Dmitry K, Tutyaeva V, Karpov V. Mapping of yeast Rpn4p transactivation domains. FEBS Lett. 2008;582:3459-64 pubmed publisher
    ..Within the N-terminus, we mapped a novel transactivation domain, which may be regulated by some modification of lysines in a proteolysis-independent manner. ..
  31. Prinz S, Avila Campillo I, Aldridge C, Srinivasan A, Dimitrov K, Siegel A, et al. Control of yeast filamentous-form growth by modules in an integrated molecular network. Genome Res. 2004;14:380-90 pubmed
    ..A module-derived hypothesis was tested. It was found that the 26S proteasome regulates filamentous-form growth. ..
  32. Park S, Li X, Kim H, Singh C, Tian G, Hoyt M, et al. Reconfiguration of the proteasome during chaperone-mediated assembly. Nature. 2013;497:512-6 pubmed publisher
    ..Thus, the Rpt-CP interface is reconfigured when the lid complex joins the nascent proteasome to form the mature holoenzyme. ..
  33. Ha S, Ju D, Xie Y. Nuclear import factor Srp1 and its associated protein Sts1 couple ribosome-bound nascent polypeptides to proteasomes for cotranslational degradation. J Biol Chem. 2014;289:2701-10 pubmed publisher
    ..or karyopherin ?) is required for ubiquitin-independent cotranslational degradation of the transcription factor Rpn4. We further demonstrate that cotranslational protein degradation is generally impaired in the srp1-49 mutant...
  34. Oling D, Eisele F, Kvint K, Nystrom T. Opposing roles of Ubp3-dependent deubiquitination regulate replicative life span and heat resistance. EMBO J. 2014;33:747-61 pubmed publisher
    ..We discuss the data in view of how heat stress and aging might elicit differential damage and challenges on the protein homeostasis network. ..
  35. Guerra Moreno A, Hanna J. Tmc1 Is a Dynamically Regulated Effector of the Rpn4 Proteotoxic Stress Response. J Biol Chem. 2016;291:14788-95 pubmed publisher
    ..The transcription factor Rpn4 mediates a key proteotoxic stress response whose best known function is to control proteasome abundance by a ..
  36. Karpov D, Tiutiaeva V, Beresten S, Karpov V. [Mapping of Rpn4p regions responsible for transcriptional activation of proteasome genes]. Mol Biol (Mosk). 2008;42:526-32 pubmed
    ..Mutant proteins were expressed in rpn4-A yeast strain and their activities were estimated by measuring the mRNA level of proteasomal genes in appropriate ..
  37. Gonzalez Ramos D, van den Broek M, van Maris A, Pronk J, Daran J. Genome-scale analyses of butanol tolerance in Saccharomyces cerevisiae reveal an essential role of protein degradation. Biotechnol Biofuels. 2013;6:48 pubmed publisher
    ..Two independently evolved n-butanol-tolerant strains carried different mutations in both RPN4 and RTG1, which encode transcription factors involved in the expression of proteasome and peroxisomal genes, ..
  38. Tomko R, Hochstrasser M. The intrinsically disordered Sem1 protein functions as a molecular tether during proteasome lid biogenesis. Mol Cell. 2014;53:433-43 pubmed publisher
    ..Thus, although Sem1 is a stoichiometric component of the mature proteasome, it has a distinct, chaperone-like function specific to early stages of proteasome assembly. ..
  39. Shirozu R, Yashiroda H, Murata S. Identification of minimum Rpn4-responsive elements in genes related to proteasome functions. FEBS Lett. 2015;589:933-40 pubmed publisher
    ..The transcription factor Rpn4 regulates concerted expression of proteasome subunits to increase the proteasome by recognizing nonamer proteasome-..
  40. Karpov D, Osipov S, Preobrazhenskaia O, Karpov V. [Rpn4p is a positive and negative transcriptional regulator of the ubiquitin-proteasome system]. Mol Biol (Mosk). 2008;42:518-25 pubmed
    ..In this work, using semiquantitative RT-PCR we have shown that deletion of RPN4 gene leads to decreasing in mRNA level of the genes of ubiqitination system RAD6, RAD23 and CDC48, while UBI4 mRNA ..
  41. Isasa M, Suñer C, Díaz M, Puig Sàrries P, Zuin A, Bichman A, et al. Cold Temperature Induces the Reprogramming of Proteolytic Pathways in Yeast. J Biol Chem. 2016;291:1664-75 pubmed publisher
    ..These unanticipated observations indicate that, during cold response, there is a proteolytic cellular reprogramming in which the proteasome acquires a role in the endocytic-vacuolar pathway. ..
  42. Shirozu R, Yashiroda H, Murata S. Proteasome Impairment Induces Recovery of Mitochondrial Membrane Potential and an Alternative Pathway of Mitochondrial Fusion. Mol Cell Biol. 2016;36:347-62 pubmed publisher
    ..Our findings demonstrate a new pathway for mitochondrial quality control that is induced by proteasome impairment. ..
  43. Spasskaia D, Karpov D, Mironov A, Karpov V. [RPN4 the yeast transcription factor promotes the complex defence against methyi, methanesulfonate]. Mol Biol (Mosk). 2014;48:166-75 pubmed
    ..It methylates bases in DNA but also leads to oxidative stress. The transcription factor Rpn4 protects yeast cells from toxic effect of MMS...
  44. Metzger M, Michaelis S. Analysis of quality control substrates in distinct cellular compartments reveals a unique role for Rpn4p in tolerating misfolded membrane proteins. Mol Biol Cell. 2009;20:1006-19 pubmed publisher
    ..Among these is RPN4, highlighting the importance of the Rpn4p-dependent response in tolerating UPR-M/C stress...
  45. Schmidt M, Haas W, Crosas B, Santamaria P, Gygi S, Walz T, et al. The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle. Nat Struct Mol Biol. 2005;12:294-303 pubmed
    ..The near-circular profile of Blm10 adapts it to the end of the CP cylinder, where it is properly positioned to activate the CP by opening the axial channel into its proteolytic chamber. ..