Mice lacking a transcriptional corepressor Tob are predisposed to cancer.
tob is a member of antiproliferative family genes. Mice lacking tob are prone to spontaneous formation of tumors. The occurrence rate of diethylnitrosamine-induced liver tumors is higher in tob(-/-) mice than in wild-type mice. tob(-/-)p53(-/-) mice show accelerated tumor formation in comparison with single null mice. Expression of cyclin D1 mRNA is increased in the absence of Tob and is reduced by Tob. Tob acts as a transcriptional corepressor and suppresses the cyclin D1 promoter activity through an interaction with histone deacetylase. Levels of tob mRNA are often decreased in human cancers, implicating tob in cancer development.
Yoshida
Yutaka
Y
Divisions of Oncology, Pathology, and Molecular Therapy, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Nakamura
Takahisa
T
Komoda
Masato
M
Satoh
Hitoshi
H
Suzuki
Toru
T
Tsuzuku
Junko K
JK
Miyasaka
Takashi
T
Yoshida
Eri H
EH
Umemori
Hisashi
H
Kunisaki
Reiko K
RK
Tani
Kenzaburo
K
Ishii
Shunsuke
S
Mori
Shigeo
S
Suganuma
Masami
M
Noda
Tetsuo
T
Yamamoto
Tadashi
T
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D020022:Genetic Predisposition to Disease; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009374:Neoplasms, Experimental / Q000209:etiology / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C098669:TOB1 protein, human; C490903:Tob1 protein, mouse; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D006655:Histone Deacetylases