E3 ubiquitin ligase Cullin4B mediated polyubiquitination of p53 for its degradation.
Controlled protein ubiquitination through E3 ubiquitin ligases and degradation via 26S proteasome machinery is required for orderly progression through cell cycle, chromatin remodeling, DNA repair, and development. Each cullin-dependent ubiquitin ligase (E3) complex can recruit various substrates for their degradation. Cullin 4A (CUL4A) and Cullin 4B (CUL4B) are members of cullin family proteins that mediate ubiquitin dependent proteolysis. Though, these two cul4 genes are functionally redundant, Cullin 4B is not a substitute for all the Cullin 4A functions. Published report has shown that CUL4A interacts with p53 and induces its decay. Although, CUL4A has been known to control several cellular processes, little is known about CUL4B functions. Therefore, in this study, we analyzed the role of CUL4B on p53 polyubiquitination. Our stable cell line and transient transfection studies show that CUL4B indeed interacts with p53 and induces its polyubiquitination. Importantly, both CUL4A and CUL4B overexpressing cells show almost equal levels of p53 polyubiquitination. Moreover, we observed an increased level of polyubiquitination on p53 in CUL4B overexpressing stable cell line upon treatment with siRNA specific for CUL4A indicating that CUL4B plays a vital role in p53 stability. In addition, we have observed the differential expression of CUL4B in various eukaryotic cell lines and mouse tissues suggesting the important role of CUL4B in various tissues. Together, these observations establish an important negative regulatory role of CUL4B on p53 stability.
Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central University, R. V. Nagar, Kalapet, 605014, Pondicherry, India.
Anand
A
Thirunavukarasou
Prachi
P
Singh
Gokulapriya
G
Govindarajalu
Venkateshwarlu
V
Bandi
Sudhakar
S
Baluchamy
D000818:Animals; D044842:Cullin Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D042822:Genomic Instability; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D059748:Proteolysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics*; D054875:Ubiquitination / Q000235:genetics
C114234:CUL4A protein, human; C517832:CUL4B protein, human; D044842:Cullin Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases