title: HCCRBP-3 induces tumorigenesis through direct interaction with HCCR-1 in human cancers.
abstract: Human cervical cancer oncogene 1, HCCR-1, is over-expressed in various human tumors and appears to serve as a negative regulator of the p53 gene. HCCR-1 transgenic mice developed breast cancers but it is unknown how HCCR-1 contributes to tumorigenesis. We identified the HCCR-1 binding protein 3 (HCCRBP-3) as a binding partner for HCCR-1. These two proteins co-localized to the mitochondria. HCCRBP-3 over-expressed in various human tumors converted normal cells into tumor cells in vitro. Nude mice injected with NIH/3T3 cells stably transfected with HCCRBP-3 also induced the tumor formation. In addition, p53 showed the functional impairment in HCCRBP-3-transfected cells as accompanied with defective induction of p21 and bax. In support of this, p21 promoter activities containing p53 responsive elements were inhibited by HCCRBP-3 in a dose-dependent manner. Therefore, our study suggests that HCCRBP-3 contributes to the HCCR-1 induced tumorigenesis by interrupting the p53 function.
authors.affiliation: Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seon Ah
authors.initials: SA
authors.lastname: Ha
authors.forename: Hyun Kee
authors.initials: HK
authors.lastname: Kim
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Yoo
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kim
authors.forename: Seung Min
authors.initials: SM
authors.lastname: Shin
authors.forename: Gi-Hwan
authors.initials: GH
authors.lastname: Gong
authors.forename: Yun Kyung
authors.initials: YK
authors.lastname: Lee
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D020218:Response Elements; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C425529:BRI3BP protein, human; D002352:Carrier Proteins; C476732:LETMD1 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53