PMID- 24452595
OWN - NLM
STAT- MEDLINE
DCOM- 20141203
LR  - 20211021
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 390
IP  - 1-2
DP  - 2014 May
TI  - E3 ubiquitin ligase Cullin4B mediated polyubiquitination of p53 for its 
      degradation.
PG  - 93-100
LID - 10.1007/s11010-014-1960-3 [doi]
AB  - 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.
FAU - Thirunavukarasou, Anand
AU  - Thirunavukarasou A
AD  - Stem Cell Laboratory, Department of Biotechnology, Pondicherry Central 
      University, R. V. Nagar, Kalapet, 605014, Pondicherry, India.
FAU - Singh, Prachi
AU  - Singh P
FAU - Govindarajalu, Gokulapriya
AU  - Govindarajalu G
FAU - Bandi, Venkateshwarlu
AU  - Bandi V
FAU - Baluchamy, Sudhakar
AU  - Baluchamy S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140123
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (CUL4A protein, human)
RN  - 0 (CUL4B protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Animals
MH  - Cullin Proteins/*genetics
MH  - Gene Expression Regulation
MH  - Genomic Instability
MH  - HEK293 Cells
MH  - Humans
MH  - Mice
MH  - Proteolysis
MH  - Tumor Suppressor Protein p53/*biosynthesis/genetics
MH  - Ubiquitin-Protein Ligases/biosynthesis/*genetics
MH  - Ubiquitination/genetics
EDAT- 2014/01/24 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/01/24 06:00
PHST- 2013/10/24 00:00 [received]
PHST- 2014/01/10 00:00 [accepted]
PHST- 2014/01/24 06:00 [entrez]
PHST- 2014/01/24 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - 10.1007/s11010-014-1960-3 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2014 May;390(1-2):93-100. doi: 10.1007/s11010-014-1960-3. Epub 
      2014 Jan 23.