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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of several Saccharomyces cerevisiae ump mutants with defects in ubiquitin (Ub)-mediated proteolysis yielded insights into the regulation of the polyubiquitin gene UBI4 and of proteasome genes. High-molecular weight Ub-protein conjugates accumulated in ump mutants with impaired proteasome function with a concomitant decrease in the amount of free Ub. 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 polyubiquitylated proteins is deleterious to cell growth. Transcription of proteasome subunit genes was induced in ump mutants affecting the proteasome, as well as under conditions that mediate DNA damage or the formation of abnormal proteins. This induction required the transcriptional activator Rpn4. Elevated Rpn4 levels in proteasome-deficient mutants or as a response to abnormal proteins were due to increased metabolic stability. Up-regulation of proteasome genes in response to DNA damage, in contrast, is shown to operate via induction of RPN4 transcription.
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PMID:Regulatory mechanisms controlling biogenesis of ubiquitin and the proteasome. 1517 33

The 26S proteasome of eukaryotic cells mediates ubiquitin-dependent as well as ubiquitin-independent degradation of proteins in many regulatory processes as well as in protein quality control. The proteasome itself is a dynamic complex with varying compositions and interaction partners. Studies in Saccharomyces cerevisiae have revealed that expression of proteasome subunit genes is coordinately controlled by the Rpn4 transcriptional activator. The cellular level of Rpn4 itself is subject to a complex regulation, which, aside of a transcriptional control of its gene, intriguingly involves ubiquitin-dependent as well as ubiquitin-independent control of its stability by the proteasome. A novel study by Ju et al. [D. Ju, H. Yu, X. Wang, Y. Xie, Ubiquitin-mediated degradation of Rpn4 is controlled by a phosphorylation-dependent ubiquitylation signal, Biochim. Biophys. Acta (in press), doi:10.1016/j.bbamcr.2007.04.012] now revealed another level of complexity by showing that phosphorylation of a specific serine residue in Rpn4 is required for its efficient targeting by the Ubr2 ubiquitin ligase.
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PMID:Biting the hand that feeds: Rpn4-dependent feedback regulation of proteasome function. 1760 55

Ubiquitin-proteasome proteolytic system participates in metabolism of the majority of intracellular proteins and regulation of key cellular processes in eukaryotes. While the structure and functioning of this system is studied rather well, a little is known about regulation of its genes expression. At present time, the only regulatory system of transcription of proteasome genes is found in the yeast Saccharomyces cerevisiae. This system includes Rpn4p-proteasome-associated transcriptional regulator and its binding site called PACE (Proteasome Associated Control Element). To learn more about function of Rpn4p as a transcriptional regulator, there are following questions: 1) is the Rpn4p regulator for PACE-containing genes which encode for components of protein ubiquitinylation system 2) what is the contribution of Rpn4p in stress-activated level of mRNA of proteasome genes. 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 level is increased in this strain. In the presence of alkylating agent methyl methanesulfonate or under heat shock we observed Rpn4 p-dependent elevation of mRNA level of the proteasomal genes RPT4 and RPNS. At the same time, CDC48 mRNA level is decreased in wild type yeast strain upon methyl methanesulfonate treatment. These data indicate that under normal or stress conditions Rpn4p may act as an activator or repressor for the genes of the ubiquitin-proteasome system.
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PMID:[Rpn4p is a positive and negative transcriptional regulator of the ubiquitin-proteasome system]. 1870 11

Most proteasome substrates are marked for degradation by ubiquitin conjugation, but some are targeted by other means. The properties of these exceptional cases provide insights into the general requirements for proteasomal degradation. Here the focus is on three ubiquitin-independent substrates that have been the subject of detailed study. These are Rpn4, a transcriptional regulator of proteasome homeostasis, thymidylate synthase, an enzyme required for production of DNA precursors and ornithine decarboxylase, the initial enzyme committed to polyamine biosynthesis. It can be inferred from these cases that proteasome association and the presence of an unstructured region are the sole prerequisites for degradation. Based on that inference, artificial substrates have been designed to test the proteasome's capacity for substrate processing and its limitations. Ubiquitin-independent substrates may in some cases be a remnant of the pre-ubiquitome world, but in other cases could provide optimized regulatory solutions. This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf.
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PMID:Ubiquitin-independent proteasomal degradation. 2368 52