L2DTL/CDT2 and PCNA Interact with p53 and Regulate p53 Polyubiquitination and Protein Stability through MDM2 and CUL4A/DDB1 Complexes

• DOI: 10.4161/cc.5.15.3150
• Publication Date: 2010-11-30T18:13:27Z
• Authors: Damon Banks; Min Wu; Leigh Ann Higa; Nadia Gavrilova; Junmin Quan; Tao Ye; Ryuji Kobayashi; Hong Sun; Hui Zhang
• Keywords: DDB1

AbstractThe CUL4-ROC1 E3 ligase complex regulates genome stability, replication, and cell cycle progression. A novel WD40 domain-containing protein, L2DTL, PCNA were identified as proteins associated with CUL4/DDB1 complexes. Inactivation of CUL4A, PCNA, DDB1, or ROC1 induced p53 stabilization growth arrest. DDB1/CUL4A complexes found to physically interact tumor suppressor its regulator MDM2/HDM2. The isolated CUL4A display potent robust polyubiquitination activity towards this is dependent on ROC1, We also that the interaction between CUL4 regulated by DNA damage. Our data further showed MDM2/HDM2 rapidly proteolyzed in response UV irradiation process PCNA. studies demonstrate DDB1-CUL4A play critical differential roles regulating protein stability unstressed stressed cells.