Linking the ubiquitin-proteasome pathway to chromatin remodeling/modification by nuclear receptors.
Over 25 years ago, eukaryotic cells were shown to contain a highly specific system for the selective degradation of short-lived proteins, this system is known as the ubiquitin-proteasome pathway. In this pathway, proteins are targeted for degradation by covalent modification by a small highly conserved protein named ubiquitin. Ubiquitin-mediated degradation of regulatory proteins plays an important role in numerous cell processes, including cell cycle progression, signal transduction and transcriptional regulation. Recent experiments have shown that the ubiquitin-proteasome pathway is also involved in nuclear hormone receptor (NR)-mediated transcriptional regulation. The idea that the ubiquitin-proteasome pathway is involved in NR-mediated transcription is strengthened by experiments showing that ubiquitin-proteasome components are recruited to NR target gene promoters. However, it is not clear how these components modulate NR-mediated chromatin remodeling and gene expression. In this review, we postulate the role of the ubiquitin-proteasome pathway on NR-mediated chromatin remodeling and gene regulation based on the current knowledge from studies implicating the pathway in chromatin structure modifications that are applicable to NR function. Since evidence from this laboratory, using the glucocorticoid receptor responsive mouse mammary tumor virus (MMTV) promoter organized as chromatin, suggest that the ubiquitin-proteasome system may be involved in the elongation phase of transcription, we particularly concentrate on chromatin modifications associated with the elongation phase.
Kinyamu
H K
HK
Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Chen
J
J
Archer
T K
TK
D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D005786:Gene Expression Regulation; D009690:Nucleic Acid Conformation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D025801:Ubiquitin / Q000378:metabolism*
D002843:Chromatin; D018160:Receptors, Cytoplasmic and Nuclear; D025801:Ubiquitin; D012319:RNA Polymerase II; D046988:Proteasome Endopeptidase Complex