Identification of a mouse cytoskeleton-associated protein, CKAP2, with microtubule-stabilizing properties.
Microtubule dynamics is an important factor in cell proliferation and one of the main targets of cancer chemotherapy. Since microtubule-associated proteins (MAPs) are known to influence microtubule stability, study of MAPs may contribute both to knowledge of cancer cell biology and to the production of new anti-cancer drugs. In this study, we identified a new mouse gene which is a homolog of human cytoskeleton-associated protein, CKAP2 gene, by differential display analysis. The level of expression of mouse CKAP2 (mCKAP2) was significantly higher in NIH3T3 cells expressing RET with a multiple endocrine neoplasia (MEN) 2A or MEN2B mutation than in parental NIH3T3 cells. Immunocytochemical analysis showed that mCKAP2 protein is localized in cytoplasm with a fibrillar appearance, and is co-localized with microtubules throughout the cell cycle. Furthermore, overexpression of mCKAP2 in cells appeared to stabilize microtubules against treatment with nocodazole, a microtubule-depolymerizing agent. In addition, levels of human CKAP2 were increased in some human tumor cell lines examined. These findings suggest that CKAP2 is a new MAP with microtubule-stabilizing properties and may represent a new molecular target for cancer chemotherapy.
Jin
Yi
Y
Department of Pathology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Murakumo
Yoshiki
Y
Ueno
Kaoru
K
Hashimoto
Mizuo
M
Watanabe
Tsuyoshi
T
Shimoyama
Yoshie
Y
Ichihara
Masatoshi
M
Takahashi
Masahide
M
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D015739:Nocodazole / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D016415:Sequence Alignment; D014162:Transfection; D014404:Tubulin / Q000235:genetics
C494575:CKAP2 protein, mouse; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D014404:Tubulin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C494999:Ret protein, mouse; D015739:Nocodazole