title: CacyBP/SIP promotes the proliferation of colon cancer cells.
abstract: CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin. We found that CacyBP/SIP was expressed in a high percentage of colon cancer cells, but not in normal colonic surface epithelium. CacyBP/SIP promoted the cell proliferation of colon cancer cells under both basal and gastrin stimulated conditions as shown by knockdown studies. Gastrin stimulation triggered the translocation of CacyBP/SIP to the nucleus, and enhanced interaction between CacyBP/SIP and SKP1, a key component of ubiquitination pathway which further mediated the proteasome-dependent degradation of p27kip1 protein. The gastrin induced reduction in p27kip1 was prevented when cells were treated with the proteasome inhibitor MG132. These results suggest that CacyBP/SIP may be promoting growth of colon cancer cells by enhancing ubiquitin-mediated degradation of p27kip1.
authors.affiliation: State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Huihong
authors.initials: H
authors.lastname: Zhai
authors.affiliation: State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Faming
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhengxiong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C491778:CACYBP protein, human; C436291:CDKN1B protein, human; D002135:Calcium-Binding Proteins; D044786:S-Phase Kinase-Associated Proteins; C097351:SKP1 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D046988:Proteasome Endopeptidase Complex