PMID- 23845142
OWN - NLM
STAT- MEDLINE
DCOM- 20140624
LR  - 20211021
IS  - 1000-467X (Print)
IS  - 1944-446X (Electronic)
IS  - 1944-446X (Linking)
VI  - 32
IP  - 9
DP  - 2013 Sep
TI  - The CUL4A ubiquitin ligase is a potential therapeutic target in skin cancer and 
      other malignancies.
PG  - 478-82
LID - 10.5732/cjc.012.10279 [doi]
AB  - Cullin 4A (CUL4A) is an E3 ubiquitin ligase that directly affects DNA repair and 
      cell cycle progression by targeting substrates including damage-specific 
      DNA-binding protein 2 (DDB2), xeroderma pigmentosum complementation group C 
      (XPC), chromatin licensing and DNA replication factor 1 (Cdt1), and p21. Recent 
      work from our laboratory has shown that Cul4a-deficient mice have greatly reduced 
      rates of ultraviolet-induced skin carcinomas. On a cellular level, 
      Cul4a-deficient cells have great capacity for DNA repair and demonstrate a slow 
      rate of proliferation due primarily to increased expression of DDB2 and p21, 
      respectively. This suggests that CUL4A promotes tumorigenesis (as well as 
      accumulation of skin damage and subsequent premature aging) by limiting DNA 
      repair activity and expediting S phase entry. In addition, CUL4A has been found 
      to be up-regulated via gene amplification or overexpression in breast cancers, 
      hepatocellular carcinomas, squamous cell carcinomas, adrenocortical carcinomas, 
      childhood medulloblastomas, and malignant pleural mesotheliomas. Because of its 
      oncogenic activity in skin cancer and up-regulation in other malignancies, CUL4A 
      has arisen as a potential candidate for targeted therapeutic approaches. In this 
      review, we outline the established functions of CUL4A and discuss the E3 ligase's 
      emergence as a potential driver of tumorigenesis.
FAU - Hannah, Jeffrey
AU  - Hannah J
AD  - Department of Pathology and Laboratory Medicine, Weill Cornell Medical College 
      and Weill Cornell Graduate School of Medical Sciences, New York, NY 10065, USA. 
      pez2001@med.cornell.edu.
FAU - Zhou, Peng-Bo
AU  - Zhou PB
LA  - eng
GR  - R01 CA098210/CA/NCI NIH HHS/United States
GR  - R56 CA098210/CA/NCI NIH HHS/United States
GR  - T32 GM008539/GM/NIGMS NIH HHS/United States
GR  - CA098210/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130712
PL  - England
TA  - Chin J Cancer
JT  - Chinese journal of cancer
JID - 101498232
RN  - 0 (CUL4A protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (DDB2 protein, human)
RN  - 0 (DNA-Binding Proteins)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Animals
MH  - Carcinogenesis/metabolism
MH  - Cell Cycle
MH  - Cell Proliferation
MH  - Cullin Proteins/genetics/*metabolism
MH  - DNA Damage
MH  - DNA Repair
MH  - DNA-Binding Proteins/metabolism
MH  - *Drug Delivery Systems
MH  - Humans
MH  - Neoplasms/genetics/metabolism
MH  - Proto-Oncogene Proteins p21(ras)/metabolism
MH  - Skin Neoplasms/genetics/*metabolism/pathology
PMC - PMC3845565
EDAT- 2013/07/13 06:00
MHDA- 2014/06/25 06:00
PMCR- 2013/09/01
CRDT- 2013/07/13 06:00
PHST- 2013/07/13 06:00 [entrez]
PHST- 2013/07/13 06:00 [pubmed]
PHST- 2014/06/25 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - cjc.012.10279 [pii]
AID - cjc-32-09-478 [pii]
AID - 10.5732/cjc.012.10279 [doi]
PST - ppublish
SO  - Chin J Cancer. 2013 Sep;32(9):478-82. doi: 10.5732/cjc.012.10279. Epub 2013 Jul 
      12.