PMID- 19962312
OWN - NLM
STAT- MEDLINE
DCOM- 20100330
LR  - 20211203
IS  - 1879-0445 (Electronic)
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 19
IP  - 23
DP  - 2009 Dec 15
TI  - ATM regulates a RASSF1A-dependent DNA damage response.
PG  - 2020-5
LID - 10.1016/j.cub.2009.10.040 [doi]
AB  - Hypermethylation of CpG islands in the RASSF1 promoter is one of the most 
      frequent events identified in human cancer. The epigenetic-driven loss of RASSF1A 
      protein expression is observed more often in tumors of higher grade and 
      correlates with a decreased responsiveness to DNA-damaging therapy. Ras 
      association domain-containing family 1A (RASSF1A) promotes apoptosis by signaling 
      through the MST2 and LATS1 kinases, leading to stabilization of the YAP1/p73 
      transcriptional complex. Here we provide evidence for a new pathway linking DNA 
      damage signaling to RASSF1A via the main sensor of double-strand breaks in cells, 
      ataxia telangiectasia mutated (ATM). We show that, upon DNA damage, RASSF1A is 
      phosphorylated by ATM on Ser131 and is involved in the activation of both MST2 
      and LATS1, leading to the stabilization of p73. Furthermore, lung and ovarian 
      tumor cell lines that retain RASSF1A expression commonly harbor polymorphisms in 
      the region of Ser131, and our analysis shows that the S131F polymorphism conveys 
      resistance to DNA-damaging agents. Thus, we present a novel DNA damage pathway 
      emanating from ATM that is frequently disabled in tumors via epigenetic silencing 
      of RASSF1 or mutation of an ATM phosphorylation site.
FAU - Hamilton, Garth
AU  - Hamilton G
AD  - Gray Institute for Radiation Oncology and Biology, University of Oxford, Old Road 
      Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
FAU - Yee, Karen S
AU  - Yee KS
FAU - Scrace, Simon
AU  - Scrace S
FAU - O'Neill, Eric
AU  - O'Neill E
LA  - eng
GR  - A9318/CRUK_/Cancer Research UK/United Kingdom
GR  - MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091203
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (RASSF1 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Ataxia Telangiectasia Mutated Proteins
MH  - Cell Cycle Proteins/*metabolism
MH  - Cell Line, Tumor
MH  - DNA Damage
MH  - DNA Repair
MH  - DNA-Binding Proteins/*metabolism
MH  - Gene Expression Regulation/*physiology
MH  - Gene Silencing
MH  - Humans
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Signal Transduction
MH  - Tumor Suppressor Proteins/genetics/*metabolism
PMC - PMC4861209
MID - EMS28698
OID - NLM: EMS28698
EDAT- 2009/12/08 06:00
MHDA- 2010/03/31 06:00
PMCR- 2016/05/09
CRDT- 2009/12/08 06:00
PHST- 2009/04/08 00:00 [received]
PHST- 2009/10/06 00:00 [revised]
PHST- 2009/10/06 00:00 [accepted]
PHST- 2009/12/08 06:00 [entrez]
PHST- 2009/12/08 06:00 [pubmed]
PHST- 2010/03/31 06:00 [medline]
PHST- 2016/05/09 00:00 [pmc-release]
AID - S0960-9822(09)01897-1 [pii]
AID - 10.1016/j.cub.2009.10.040 [doi]
PST - ppublish
SO  - Curr Biol. 2009 Dec 15;19(23):2020-5. doi: 10.1016/j.cub.2009.10.040. Epub 2009 
      Dec 3.