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Homeostatic regulation of the proteasome via an Rpn4-dependent feedback circuit.
Biochem Biophys Res Commun. 2004 Aug 13; 321(1):51-7.BB

Abstract

The 26S proteasome is a complex protease consisting of at least 32 different subunits. 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 by the 26S proteasome. These observations suggested that in vivo proteasome abundance may be regulated by an Rpn4-dependent feedback circuit. Here, we present direct evidence to support the Rpn4-proteasome feedback model. We show that proteasome expression is increased when proteasome activity is impaired, and that this increase is Rpn4-dependent. Moreover, we demonstrate that expression of a stable form of Rpn4 leads to elevation of proteasome expression. Our data also reveal that the Rpn4-proteasome feedback circuit is critical for cell growth when proteasome activity is compromised, and plays an important role in response to DNA damage. This study provides important insights into the mechanism underlying proteasome homeostasis.

Authors+Show Affiliations

Ju D
Barbara Ann Karmanos Cancer Institute, Department of Pathology, Wayne State University School of Medicine, 110 Warren Avenue, Detroit, MI 48201, USA.
Wang L
No affiliation info available
Mao X
No affiliation info available
Xie Y
No affiliation info available

MeSH

DNA-Binding ProteinsFeedbackGenotypeKineticsPeptide HydrolasesProteasome Endopeptidase ComplexProtein SubunitsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTrans-ActivatorsTranscription FactorsZinc Fingers

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15358214

Citation

Ju, Donghong, et al. "Homeostatic Regulation of the Proteasome Via an Rpn4-dependent Feedback Circuit." Biochemical and Biophysical Research Communications, vol. 321, no. 1, 2004, pp. 51-7.
Ju D, Wang L, Mao X, et al. Homeostatic regulation of the proteasome via an Rpn4-dependent feedback circuit. Biochem Biophys Res Commun. 2004;321(1):51-7.
Ju, D., Wang, L., Mao, X., & Xie, Y. (2004). Homeostatic regulation of the proteasome via an Rpn4-dependent feedback circuit. Biochemical and Biophysical Research Communications, 321(1), 51-7.
Ju D, et al. Homeostatic Regulation of the Proteasome Via an Rpn4-dependent Feedback Circuit. Biochem Biophys Res Commun. 2004 Aug 13;321(1):51-7. PubMed PMID: 15358214.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homeostatic regulation of the proteasome via an Rpn4-dependent feedback circuit. AU - Ju,Donghong, AU - Wang,Li, AU - Mao,Xicheng, AU - Xie,Youming, PY - 2004/06/17/received PY - 2004/9/11/pubmed PY - 2004/11/13/medline PY - 2004/9/11/entrez SP - 51 EP - 7 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 321 IS - 1 N2 - The 26S proteasome is a complex protease consisting of at least 32 different subunits. 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 by the 26S proteasome. These observations suggested that in vivo proteasome abundance may be regulated by an Rpn4-dependent feedback circuit. Here, we present direct evidence to support the Rpn4-proteasome feedback model. We show that proteasome expression is increased when proteasome activity is impaired, and that this increase is Rpn4-dependent. Moreover, we demonstrate that expression of a stable form of Rpn4 leads to elevation of proteasome expression. Our data also reveal that the Rpn4-proteasome feedback circuit is critical for cell growth when proteasome activity is compromised, and plays an important role in response to DNA damage. This study provides important insights into the mechanism underlying proteasome homeostasis. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/15358214/Homeostatic_regulation_of_the_proteasome_via_an_Rpn4_dependent_feedback_circuit_ DB - PRIME DP - Unbound Medicine ER -