TSC-box is essential for the nuclear localization and antiproliferative effect of XTSC-22

Akiko Hashiguchi, Keisuke Hitachi, Masafumi Inui, Koji Okabayashi, Makoto Asashima

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Transforming growth factor-β1-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.

Original languageEnglish
Pages (from-to)197-204
Number of pages8
JournalDevelopment Growth and Differentiation
Volume49
Issue number3
DOIs
Publication statusPublished - 01-04-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

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