Ubiquitin-independent degradation of cell-cycle inhibitors by the REGgamma proteasome.
The cell-cycle regulator p21(Cip1) is degraded by proteasomes independently of ubiquitination. We now show that degradation of p21 in vivo does not require the 19S proteasome lid, which contains the ubiquitin-binding subunit. Instead, the major proteasomal pathway for p21 degradation involves an alternative proteasome lid, the REGgamma complex. REGgamma binds ... to p21 in vivo, and deletion of p21's REGgamma-binding site greatly extends its half-life. Knockdown of REGgamma by RNA interference stabilizes p21, p21 has a significantly extended half-life in REGgamma(-/-) murine embryonic fibroblasts, and the p21 abundance is elevated in REGgamma(-/-) mice. The role of REGgamma in cell-cycle regulation may extend beyond p21 regulation, because p16(INK4A) and p19(Arf) also bind to REGgamma and are stabilized in REGgamma-deficient cells.
Mesh Terms:
ADP-Ribosylation Factors, Animals, Autoantigens, Cell Line, Cell Line, Transformed, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p21, Embryo, Mammalian, Fibroblasts, Humans, Mice, Mice, Knockout, Proteasome Endopeptidase Complex, Protein Binding, RNA, Small Interfering, Ubiquitin
ADP-Ribosylation Factors, Animals, Autoantigens, Cell Line, Cell Line, Transformed, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p21, Embryo, Mammalian, Fibroblasts, Humans, Mice, Mice, Knockout, Proteasome Endopeptidase Complex, Protein Binding, RNA, Small Interfering, Ubiquitin
Mol. Cell
Date: Jun. 22, 2007
PubMed ID: 17588519
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