Tob proteins suppress steroid hormone receptor-mediated transcriptional activation

Hisaya Kawate, Yin Wu, Keizo Ohnaka, Hajime Nawata, Ryoichi Takayanagi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Although sex steroid hormones have significant effects on bone metabolism, the molecular mechanisms of these actions have not been fully elucidated yet. We examined the functional relationship between steroid hormone receptors and Tob, a member of an anti-prolifelative protein family and a negative regulator of osteoblast proliferation and differentiation. Luciferase assay using promoters carrying hormone-responsive elements revealed that both Tob1 and Tob2 proteins but not PC3 suppressed steroid hormone receptor-dependent transcriptional activation in MC3T3-E1 osteoblastic cells. Mutated Tob proteins carrying amino acid substitutions at an LXXLL motif also showed the same degree of inhibition of the transcriptional activation as the wild type. By observation of androgen receptor (AR)-tagged with green fluorescent protein under a confocal laser scanning microscope, we found that Tob1 inhibits the nuclear foci formation of dihydrotestosterone-bound AR. These results indicate that Tob family proteins may negatively regulate sex steroid hormone action in bone formation.

Original languageEnglish
Pages (from-to)77-86
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume230
Issue number1-2
DOIs
Publication statusPublished - Jan 31 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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