Open AccessRegulation of c‐ MYC transcriptional activity by transforming growth factor‐beta 1‐stimulated clone 22
Author(s) -
Zheng Ling,
Suzuki Hiroyuki,
Nakajo Yuka,
Nakano Akinobu,
Kato Mitsuyasu
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13466
Subject(s) - biology , transcription factor , cell growth , microbiology and biotechnology , promoter , cyclin dependent kinase , carcinogenesis , transforming growth factor beta , telomerase , embryonic stem cell , gene , transforming growth factor , gene expression , cell cycle , genetics
c‐ MYC stimulates cell proliferation through the suppression of cyclin‐dependent kinase ( CDK ) inhibitors including P15 ( CDKN 2B ) and P21 ( CDKN 1A ). It also activates E‐box‐mediated transcription of various target genes including telomerase reverse transcriptase ( TERT ) that is involved in cellular immortality and tumorigenesis. Transforming growth factor‐beta 1 ( TGF ‐β1)‐stimulated clone 22 ( TSC ‐22/ TSC 22D1 ) encodes a highly conserved leucine zipper protein that is induced by various stimuli, including TGF ‐β. TSC ‐22 inhibits cell growth in mammalian cells and in Xenopus embryos. However, underlying mechanisms of growth inhibition by TSC ‐22 remain unclear. Here, we show that TSC ‐22 physically interacts with c‐ MYC to inhibit the recruitment of c‐ MYC on the P15 ( CDKN 2B ) and P21 ( CDKN 1A ) promoters, effectively inhibiting c‐ MYC ‐mediated suppression of P15 ( CDKN 2B ) and also P21 ( CDKN 1A ) promoter activities. In contrast, TSC ‐22 enhances c‐ MYC ‐mediated activation of the TERT promoter. Additionally, the expression of TSC ‐22 in embryonic stem cells inhibits cell growth without affecting its pluripotency‐related gene expression. These results indicate that TSC ‐22 differentially regulates c‐ MYC ‐mediated transcriptional activity to regulate cell proliferation.