title: DNA damage regulates ARID1A stability via SCF ubiquitin ligase in gastric cancer cells.
abstract: OBJECTIVE
  The gene product of the AT-rich interactive domain 1A (SWI-like) gene (ARID1A) is a member of the SWI/SNF adenosine triphosphate-dependent chromatin-remodeling complexes, which plays an essential role in controlling gene expression and is also involved in cancer development. ARID1A is frequently mutated in a wild variety of cancers and function as a tumor suppressor in several kinds of cancers. ARID1A was down-regulated in gastric cancer, and associated poor patient prognosis. However, how ARID1A protein is regulated in gastric cancer remains largely unknown.
  
  
  METHODS
  Here, we show that ARID1A protein is rapidly ubiquitinated and degradated in gastric cancer cells in response to DNA damage treatment.
  
  
  RESULTS
  Using genetic and pharmacologic Cullin inactivation coupled with in vitro ubiquitination assay, we demonstrate that ARID1A is a substrate of the Cullin-SKP1-F-box protein (SCF) complexes. Moreover, gastric cancer cells with forced expression of ARID1A showed an increased sensitivity to DNA damage reagents. Thus, our data uncovered a previous unknown posttranscriptional regulation of ARID1A by SCF E3 ligase in gastric cancer cells in DNA damage response.
  
  
  CONCLUSIONS
  These findings suggest ARID1A might be a promising drug target in gastric cancer treatment.
authors.affiliation: Department of Gastrointestinal Surgery, and Department of Gastroenterology, Ningbo Medical Center, Li Huili Hospital, Ningbo, Zhejiang, China. Jiang-zhouhua@hotmail.com.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Jiang
authors.forename: X-W
authors.initials: XW
authors.lastname: Dong
authors.forename: Y-C
authors.initials: YC
authors.lastname: Shen
authors.forename: H-L
authors.initials: HL
authors.lastname: Qian
authors.forename: M
authors.initials: M
authors.lastname: Yan
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Yu
authors.forename: H-B
authors.initials: HB
authors.lastname: He
authors.forename: C-D
authors.initials: CD
authors.lastname: Lu
authors.forename: F
authors.initials: F
authors.lastname: Qiu
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics*; D004268:DNA-Binding Proteins; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D044843:SKP Cullin F-Box Protein Ligases