Tob proteins suppress steroid hormone receptor-mediated transcriptional activation.
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-proliferative 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.
Kawate
Hisaya
H
Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Wu
Yin
Y
Ohnaka
Keizo
K
Nawata
Hajime
H
Takayanagi
Ryoichi
R
D020816:Amino Acid Motifs; D059002:Androgen Receptor Antagonists; D000818:Animals; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000737:chemistry; D002522:Chlorocebus aethiops; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D051379:Mice; D009154:Mutation / Q000235:genetics; D010006:Osteoblasts / Q000737:chemistry / Q000378:metabolism*; D011944:Receptors, Androgen / Q000032:analysis / Q000235:genetics; D020218:Response Elements / Q000235:genetics / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D059002:Androgen Receptor Antagonists; D018797:Cell Cycle Proteins; D047628:Estrogen Receptor alpha; D047908:Intracellular Signaling Peptides and Proteins; D011944:Receptors, Androgen; C098669:TOB1 protein, human; C402648:TOB2 protein, human; D025521:Tumor Suppressor Proteins; D008156:Luciferases