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TSC‐box is essential for the nuclear localization and antiproliferative effect of XTSC‐22
Author(s) -
Hashiguchi Akiko,
Hitachi Keisuke,
Inui Masafumi,
Okabayashi Koji,
Asashima Makoto
Publication year - 2007
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/j.1440-169x.2007.00908.x
Subject(s) - nuclear localization sequence , biology , microbiology and biotechnology , nucleus
Transforming growth factor‐ β 1‐stimulated clone 22 (TSC‐22) encodes a leucine zipper‐containing protein that is highly conserved among various species. Mammalian TSC‐22 is a potential tumor suppressor gene. It translocates into nuclei and suppresses cell division upon antiproliferative stimuli. In human colon carcinoma cells, TSC‐22 inhibits cell growth by upregulating expression of the p21 gene, a cyclin‐dependent kinase (Cdk) inhibitor. We previously showed that the Xenopus laevis homologue of the TSC‐22 gene ( XTSC‐22 ) is required for cell movement during gastrulation through cell cycle regulation. In this report, we investigated the molecular mechanism of the antiproliferative effect of XTSC‐22. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis suggested that XTSC‐22 did not affect the expression levels of the p21 family of Cdk inhibitors or other cell cycle regulators. Analysis of deletion mutants of XTSC‐22 revealed that nuclear localization of the N‐terminal TSC‐box is necessary for cell cycle inhibition by XTSC‐22. Further experiments suggested that p27Xic1, a key Cdk inhibitor in Xenopus , interacts with XTSC‐22. Because p27Xic1 is a cell cycle inhibitor with a nuclear localization signal, it is possible that XTSC‐22 suppresses cell division by translocating into the nucleus with p27Xic1, where it may potentiate the intranuclear action of p27Xic1.