title: C-Terminal Binding Protein is Involved in Promoting to the Carcinogenesis of Human Glioma.
abstract: C-terminal binding protein (CtBP) is responsible for regulating the pathogenesis of a lot of cancer types. However, whether CtBP1/2 is involved in regulating the growth and development of human glioma is still obscure. In the present study presented here, our results firstly reveal that CtBP1/2 deficiency, induced by siRNA interference, disrupts the functional integrity of the MRN complex that is responsible for DNA repair in human glioma cells. The dysfunction of the MRN complex further contributes to the up-regulation of ATM and Rad3-related kinase (ATR) and Chk1 signaling pathway, which inhibits cell cycle progression mediated by CDK2, preparing for the initiation of DNA repair. Under the condition of hypoxia, hypoxia-inducible factor-1α (HIF-1α) can be directly regulated by CDK2 on protein level, playing coordinately regulatory role in the carcinogenesis of human glioma cells. Overall, our findings reveal that CtBP1/2 is essential to promote to human glioma cell growth through maintaining the DNA stability regulated by the MRN/ATR/Chk1/CDK2/HIF-1α signaling pathway.
authors.affiliation: Otorhinolaryngology-Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Otorhinolaryngology-Head & Neck Surgery, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA. lijundi1978um@hotmail.com.
authors.forename: Gloria
authors.initials: G
authors.lastname: Di
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein
keywords: Cell cycle; CtBP; DNA damage; Oncogenesis; Transcriptional regulation