TGF-beta signals the formation of a unique NF1/Smad4-dependent transcription repressor-complex in human diploid fibroblasts
2011 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 411, no 3, 648-653 p.Article in journal (Refereed) Published
We earlier reported the formation of a unique nuclear NF1/Smad complex in serum-restricted fibroblasts that acts as an NF1-dependent repressor of the human adenine nucleotide translocase-2 gene (ANT2) [K. Luciakova, G. Kollarovic, P. Barath, B.D. Nelson, Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex, Biochem. J. 412 (2008) 123-130]. In the present study, we show that TGF-beta, like serum-restriction: (a) induces the formation of NF1/Smad repressor complexes, (b) increases binding of the complexes to the repressor elements (Go elements) in the ANT2 promoter, and (c) inhibits ANT2 expression. Repression of ANT2 by TGF-beta is eliminated by mutating the NF1 binding sites in the Go repressor elements. All of the above responses to TGF-beta are prevented by inhibitors of TGF-beta RI and MAPK p38. These inhibitors also prevent NF1/Smad4 repressor complex formation and repression of ANT2 expression in serum-restricted cells, suggesting that similar signaling pathways are initiated by TGF-beta and serum-restriction. The present finding that NF1/Smad4 repressor complexes are formed through TGF-beta signaling pathways suggests a new, but much broader, role for these complexes in the initiation or maintenance of the growth-inhibited state.
Place, publisher, year, edition, pages
2011. Vol. 411, no 3, 648-653 p.
Adenine nucleotide translocator-2, NF1, Repression, Transforming growth factor-1, p38 MAPK, TGF-beta RI
IdentifiersURN: urn:nbn:se:su:diva-68301DOI: 10.1016/j.bbrc.2011.07.017ISI: 000294309800030OAI: oai:DiVA.org:su-68301DiVA: diva2:477557
authorCount :52012-01-132012-01-032012-01-13Bibliographically approved