Isolation and characterization of a novel gene CLUAP1 whose expression is frequently upregulated in colon cancer.
To disclose mechanisms of colorectal carcinogenesis and identify novel diagnostic markers and drug targets for treatment of these tumors, we previously analysed the expression profiles of 11 colorectal cancers using a genome-wide cDNA microarray containing 23,040 genes. Among the genes commonly transactivated in the cancers, we identified a novel human gene, which we termed CLUAP1 (clusterin-associated protein 1). It encodes a nuclear protein of 413 amino acids containing a coiled-coil domain. To investigate its function, we searched for CLUAP1-interacting proteins using yeast two-hybrid system and identified nuclear Clusterin. Expression of CLUAP1 was gradually increased in the late S to G2/M phases of cell cycle and it returned to the basal level in the G0/G1 phases. Suppression of this gene by short interfering RNAs resulted in growth retardation in the transfected cells. These data provide better understanding of colorectal carcinogenesis, and inactivation of CLUAP1 may conceivably serve in the future as a novel therapeutic intervention for treatment of colon cancer.
Takahashi
Meiko
M
1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo 108-8639, Japan.
Lin
Yu-Min
YM
Nakamura
Yusuke
Y
Furukawa
Yoichi
Y
D000595:Amino Acid Sequence; D001483:Base Sequence; D051152:Clusterin; D003110:Colonic Neoplasms / Q000235:genetics*; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation
C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones