Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O15164 (tripartite motif-containing 24)
 26 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma GH profiles regulate the sexually dimorphic expression of cytochromes P450 and many other genes in rat and mouse liver; however, the proximal transcriptional regulators of these genes are unknown. Presently, we characterize three liver transcription factors that are expressed in adult female rat and mouse liver at levels up to 16-fold [thymus high-mobility group box protein (Tox)], 73-fold [tripartite motif-containing 24 (Trim24)/transcription initiation factor-1alpha (TIF1alpha)], and 125-fold [cut-like 2 (Cutl2)/cut homeobox 2 (Cux2)] higher than in adult males, depending on the strain and species, with Tox expression only detected in mice. In rats, these sex differences first emerged at puberty, when the high prepubertal expression of Cutl2 and Trim24 was extinguished in males but was further increased in females. Rat hepatic expression of Cutl2 and Trim24 was abolished by hypophysectomy and, in the case of Cutl2, was restored to near-female levels by continuous GH replacement. Cutl2 and Trim24 were increased to female-like levels in livers of intact male rats and mice treated with GH continuously (female GH pattern), whereas Tox expression reached only about 40% of adult female levels. Expression of all three genes was also elevated to normal female levels or higher in male mice whose plasma GH profile was feminized secondary to somatostatin gene disruption. Cutl2 and Trim24 both responded to GH infusion in mice within 10-24 h and Tox within 4 d, as compared with at least 4-7 d required for the induced expression of several continuous GH-regulated cytochromes P450 and other female-specific hepatic genes. Cutl2, Trim24, and Tox were substantially up-regulated in livers of male mice deficient in either of two transcription factors implicated in GH regulation of liver sex specificity, namely, signal transducer and activator of transcription 5b (STAT5b) and hepatocyte nuclear factor 4alpha (HNF4alpha), with sex-specific expression being substantially reduced or lost in mice deficient in either nuclear factor. Cutl2 and Trim24 both display transcriptional repressor activity and could thus contribute to the loss of GH-regulated, male-specific liver gene expression seen in male mice deficient in STAT5b or HNF4alpha. Binding sites for Cutl1, whose DNA-binding specificity is close to that of Cutl2, were statistically overrepresented in STAT5b-dependent male-specific mouse genes, lending support to this hypothesis.
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PMID:Characterization of three growth hormone-responsive transcription factors preferentially expressed in adult female liver. 1741 18

Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis. Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis. We here show that, in humans, Gfi-1B controls the development of erythrocytes and megakaryocytes by regulating the proliferation and differentiation of bipotent erythro-megakaryocytic progenitors. We further identify in this cell population the type III transforming growth factor-beta receptor gene, TGFBR3, as a direct target of Gfi-1B. Knockdown of Gfi-1B results in altered transforming growth factor-beta (TGF-beta) signaling as shown by the increase in Smad2 phosphorylation and its inability to associate to the transcription intermediary factor 1-gamma (TIF1-gamma). Because the Smad2/TIF1-gamma complex is known to specifically regulate erythroid differentiation, we propose that, by repressing TGF-beta type III receptor (TbetaRIotaII) expression, Gfi-1B favors the Smad2/TIF1-gamma interaction downstream of TGF-beta signaling, allowing immature progenitors to differentiate toward the erythroid lineage.
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PMID:Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage. 2012 15