A role for the cyclin box in the ubiquitin-mediated degradation of cyclin G1.
Cyclin G1 was identified as a transcriptional target of p53 that encodes a protein with strong homology to the cyclin family of cell cycle regulators. We show that either ectopically expressed or endogenous cyclin G1 protein is very unstable, undergoes modification with ubiquitin, and is likely degraded by the proteasome. Ectopic cyclin G1 protein stability is increased by cyclin box mutation or by association with inactive cyclin-dependent kinase (CDK) subunits, suggesting that a function of cyclin G1 as a CDK regulator may be required for its rapid turnover. Furthermore, cyclin G1 and the cyclin box mutant interact with and are ubiquitinated by MDM2, another transcriptional target of p53 that acts as a negative regulator of p53 stability. These data suggest that the cyclin box has a role in the proteasome-mediated degradation of cyclin G1 and thus suggest a putative role for a CDK in cyclin G1 metabolism and function.
Piscopo
Denise M
DM
Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, USA.
Hinds
Philip W
PW
D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism; D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
C534702:CCNG1 protein, human; C534703:Ccng1 protein, mouse; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D046988:Proteasome Endopeptidase Complex; D020823:ADP-Ribosylation Factor 1