title: Cullin 4A associates with the UV-damaged DNA-binding protein DDB.
abstract: The damaged DNA-binding protein (DDB) is believed to be involved in DNA repair, and it has been linked to the repair deficiency disease xeroderma pigmentosum. DDB also exhibits transcriptional activities. DDB binds to the activation domain of E2F1 and stimulates E2F1-activated transcription. Here we provide evidence that DDB or DDB-associated proteins are targets of cullin 4A (CUL-4A). CUL-4A is a member of the cullin family of proteins, which are believed to be ubiquitin-protein isopeptide ligases (type E3). The CUL-4A gene has been shown to be amplified and up-regulated in breast carcinomas. In this study, we identify CUL-4A as one of the DDB-associated proteins. CUL-4A co-immunoprecipitates with DDB, but not with a naturally occurring mutant of DDB. Moreover, CUL-4A in HeLa nuclear extracts co-purifies with DDB, suggesting they are parts of the same complex. The observation provides insights how CUL-4A, through an interaction with DDB, might be playing a role in the development of breast carcinomas.
authors.affiliation: Department of Biochemistry, University of Illinois, Chicago, Illinois 60612, USA.
authors.forename: P
authors.initials: P
authors.lastname: Shiyanov
authors.forename: A
authors.initials: A
authors.lastname: Nag
authors.forename: P
authors.initials: P
authors.lastname: Raychaudhuri
mesh_terms: D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002846:Chromatography, Affinity; D044842:Cullin Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012516:Osteosarcoma; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
chemical_list: C114234:CUL4A protein, human; D044842:Cullin Proteins; C091435:DDB1 protein, human; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins