The MDM2 RING finger is required for cell cycle-dependent regulation of its protein expression.
The MDM2 oncoprotein is overexpressed in many human tumors and cancers. MDM2 functions as an E3 ligase for p53 and for itself. MDM2 also interacts with the retinoblastoma protein (RB) and the transcription factor E2F1 to promote cell cycle S-phase entry. Here, we report that MDM2 protein expression is cell cycle-regulated, which is dependent on its RING finger domain and requires Lys446. We show that MDM2 protein is stabilized at S phase. In addition, overexpression of MDM2 results in stimulation of E2F activity and accumulation of cells in S phase. These data suggest that ubiquitination of MDM2 is cell cycle-regulated and that MDM2 may play a role in cell cycle progression.
Gu
Ling
L
Department of Biochemistry, Boston University School of Medicine, 715 Albany Street, K423, MA 02118, USA.
Ying
Haoqiang
H
Zheng
Hongwu
H
Murray
Stephen A
SA
Xiao
Zhi-Xiong Jim
ZX
D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002469:Cell Separation; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D009687:Nuclear Proteins; D017434:Protein Structure, Tertiary; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D051736:Proto-Oncogene Proteins c-mdm2; D016196:S Phase; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D003513:Cycloheximide; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D008239:Lysine