PMID- 31210753
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 1475-2867 (Print)
IS  - 1475-2867 (Electronic)
IS  - 1475-2867 (Linking)
VI  - 19
DP  - 2019
TI  - DNA damage-induced activation of ATM promotes beta-TRCP-mediated ARID1A 
      ubiquitination and destruction in gastric cancer cells.
PG  - 162
LID - 10.1186/s12935-019-0878-y [doi]
LID - 162
AB  - BACKGROUND: AT-rich interactive domain-containing protein 1A (ARID1A) is a 
      subunit of the mammary SWI/SNF chromatin remodeling complex and a tumor 
      suppressor protein. The loss of ARID1A been observed in several types of human 
      cancers and associated with poor patient prognosis. Previously, we have reported 
      that ARID1A protein was rapidly ubiquitinated and destructed in gastric cancer 
      cells during DNA damage response. However, the ubiquitin e3 ligase that mediated 
      this process remains unclear. MATERIALS AND METHODS: The interaction between 
      ARID1A and beta-TRCP was verified by co-immunoprecipitation (Co-IP) assay. The 
      degron site of ARID1A protein was analyzed by bioinformatics assay. Short hairpin 
      RNAs (shRNAs) were used to knockdown (KD) gene expression. RESULTS: Here we show 
      that DNA damage promotes ARID1A ubiquitination and subsequent destruction via the 
      ubiquitin E3 ligase complex SCFbeta-TRCP. beta-TRCP recognizes ARID1A through a 
      canonical degron site (DSGXXS) after its phosphorylation in response to DNA 
      damage. Notably, genetic inactivation of the Ataxia Telangiectasia Mutated (ATM) 
      kinase impaired DNA damage-induced ARID1A destruction. CONCLUSIONS: Our studies 
      provide a novel molecular mechanism for the negative regulation of ARID1A by 
      beta-TRCP and ATM in DNA damaged gastric cancer cells.
FAU - Jiang, Zhou-Hua
AU  - Jiang ZH
AD  - 1Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang China. ISNI: 
      0000 0004 1759 700X. GRID: grid.13402.34
AD  - Department of Gastrointestinal Surgery, Ningbo Medical Center, Li Huili Eastern 
      Hospital, Ningbo, 315000 Zhejiang China.
FAU - Peng, Tao
AU  - Peng T
AD  - Department of Gastrointestinal Surgery, Ningbo Medical Center, Li Huili Eastern 
      Hospital, Ningbo, 315000 Zhejiang China.
FAU - Qian, Hai-Long
AU  - Qian HL
AD  - Department of Gastrointestinal Surgery, Ningbo Medical Center, Li Huili Eastern 
      Hospital, Ningbo, 315000 Zhejiang China.
FAU - Lu, Cai-de
AU  - Lu CD
AD  - Department of Gastrointestinal Surgery, Ningbo Medical Center, Li Huili Eastern 
      Hospital, Ningbo, 315000 Zhejiang China.
FAU - Qiu, Feng
AU  - Qiu F
AD  - Department of Gastrointestinal Surgery, Ningbo Medical Center, Li Huili Eastern 
      Hospital, Ningbo, 315000 Zhejiang China.
FAU - Zhang, Su-Zhan
AU  - Zhang SZ
AD  - 3Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang 
      University School of Medicine, Hangzhou, 310009 Zhejiang China. GRID: 
      grid.412465.0
LA  - eng
PT  - Journal Article
DEP - 20190614
PL  - England
TA  - Cancer Cell Int
JT  - Cancer cell international
JID - 101139795
PMC - PMC6567580
OTO - NOTNLM
OT  - ARID1A
OT  - DNA damage
OT  - Phosphodegron
OT  - beta-TRCP
COIS- Competing interestsThe authors declare that they have no competing interests.
EDAT- 2019/06/19 06:00
MHDA- 2019/06/19 06:01
PMCR- 2019/06/14
CRDT- 2019/06/19 06:00
PHST- 2019/03/20 00:00 [received]
PHST- 2019/06/03 00:00 [accepted]
PHST- 2019/06/19 06:00 [entrez]
PHST- 2019/06/19 06:00 [pubmed]
PHST- 2019/06/19 06:01 [medline]
PHST- 2019/06/14 00:00 [pmc-release]
AID - 878 [pii]
AID - 10.1186/s12935-019-0878-y [doi]
PST - epublish
SO  - Cancer Cell Int. 2019 Jun 14;19:162. doi: 10.1186/s12935-019-0878-y. eCollection 
      2019.