PMID- 15548678 OWN - NLM STAT- MEDLINE DCOM- 20050224 LR - 20161124 IS - 0008-5472 (Print) IS - 0008-5472 (Linking) VI - 64 IP - 22 DP - 2004 Nov 15 TI - Cul4A physically associates with MDM2 and participates in the proteolysis of p53. PG - 8152-5 AB - The cullin 4A (Cul4A) gene is amplified and overexpressed in breast and hepatocellular carcinomas. Cul4A functions as an E3 ligase and participates in the proteolysis of several regulatory proteins through the ubiquitin-proteasome pathway. Here, we show that Cul4A associates with MDM2 and p53. Depletion of Cul4A leads to an accumulation of p53. Moreover, expression of Cul4A increases the decay-rate of p53 and delays the accumulation of p53 in response to DNA damage. Cul4A fails to increase the decay of p53 in mouse embryonic fibroblasts lacking MDM2. In addition, the Cul4A-mediated rapid decay of p53 is blocked by p19ARF. The results provide evidence for a role of Cul4A in the MDM2-mediated proteolysis of p53. FAU - Nag, Alo AU - Nag A AD - Department of Biochemistry and Molecular Genetics, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois 60607, USA. FAU - Bagchi, Srilata AU - Bagchi S FAU - Raychaudhuri, Pradip AU - Raychaudhuri P LA - eng GR - CA88863/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cancer Res JT - Cancer research JID - 2984705R RN - 0 (CUL4A protein, human) RN - 0 (Cullin Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.3.2.27 (MDM2 protein, human) RN - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2) SB - IM MH - Cullin Proteins/*metabolism MH - HeLa Cells MH - Humans MH - Hydrolysis MH - Nuclear Proteins/*metabolism MH - Protein Binding MH - Proto-Oncogene Proteins/*metabolism MH - Proto-Oncogene Proteins c-mdm2 MH - Tumor Suppressor Protein p53/*metabolism EDAT- 2004/11/19 09:00 MHDA- 2005/02/25 09:00 CRDT- 2004/11/19 09:00 PHST- 2004/11/19 09:00 [pubmed] PHST- 2005/02/25 09:00 [medline] PHST- 2004/11/19 09:00 [entrez] AID - 64/22/8152 [pii] AID - 10.1158/0008-5472.CAN-04-2598 [doi] PST - ppublish SO - Cancer Res. 2004 Nov 15;64(22):8152-5. doi: 10.1158/0008-5472.CAN-04-2598.