A role for Rad23 proteins in 26S proteasome-dependent protein degradation?

Mutat Res. 2002 Jan 29;499(1):53-61. doi: 10.1016/s0027-5107(01)00291-3.

Abstract

Treatment of cells with genotoxic agents affects protein degradation in both positive and negative ways. Exposure of S. cerevisiae to the alkylating agent MMS resulted in activation of genes that are involved in ubiquitin- and 26S proteasome-dependent protein degradation. This process partially overlaps with the activation of the ER-associated protein degradation pathway. The DNA repair protein Rad23p and its mammalian homologues have been shown to inhibit degradation of specific substrates in response to DNA damage. Particularly the recently identified inhibition of degradation by mouse Rad23 protein (mHR23) of the associated nucleotide excision repair protein XPC was shown to stimulate DNA repair.Recently, it was shown that Rad23p and the mouse homologue mHR23B also associate with Png1p, a deglycosylation enzyme. Png1p-mediated deglycosylation plays a role in ER-associated protein degradation after accumulation of malfolded proteins in the endoplasmic reticulum. Thus, if stabilization of proteins that are associated with the C-terminus of Rad23p is a general phenomenon, then Rad23 might be implicated in the stimulation of ER-associated protein degradation as well. Interestingly, the recently identified HHR23-like protein Mif1 is also thought to play a role in ER-associated protein degradation. The MIF1 gene is strongly activated in response to ER-stress. Mif1 contains a ubiquitin-like domain which is most probably involved in binding to S5a, a subunit of the 19S regulatory complex of the 26S proteasome. On the basis of its localization in the ER-membrane, it is hypothesized that Mif1 could play a role in the translocation of the 26S proteasome towards the ER-membrane, thereby enhancing ER-associated protein degradation.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacterial Proteins*
  • DNA Damage / drug effects
  • DNA Damage / physiology*
  • DNA Repair Enzymes
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Methyl Methanesulfonate / pharmacology
  • Peptide Hydrolases / metabolism*
  • Polyubiquitin / metabolism
  • Proteasome Endopeptidase Complex*
  • Protein Serine-Threonine Kinases*
  • Proteins / metabolism*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Subtilisins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • Membrane Glycoproteins
  • Proteins
  • RAD23 protein, S cerevisiae
  • RPN4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Polyubiquitin
  • RAD23A protein, human
  • Methyl Methanesulfonate
  • IRE1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Peptide Hydrolases
  • HreP protein, Yersinia enterocolitica
  • Subtilisins
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease
  • DNA Repair Enzymes