Transforming Growth Factor β-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC

ABSTRACT

Recognition of gene promoters by RNA polymerase II is mediated by general transcription factor IID (TFIID), which has been thought to be a static complex and to play a passive role in the regulation of gene expression under the instruction of gene-specific transcription factors. Here we show that transforming growth factor β (TGF-β) induced degradation of the TFIID subunit TAF7 in cultured mouse mammary epithelial cells and that this effect was required for proliferative arrest in response to TGF-β stimulation. TGF-β stimulated transcription of the gene for the ubiquitin ligase TRIM26, which was shown to ubiquitylate TAF7 and thereby to target it for proteasomal degradation. Sustained exposure of cells to TGF-β resulted in recovery from proliferative arrest in association with amplification of the Myc proto-oncogene, with MYC inhibiting TRIM26 induction by TGF-β. Our data thus show that TFIID is not simply a general mediator of transcription but contributes to the regulation of transcription in response to cell stimulation, playing a key role in the cytostatic function of TGF-β.

KEYWORDS:

• MYC
• TAF7
• TGF-β
• TRIM26
• proliferation arrest
• ubiquitylation

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at https://doi.org/10.1128/MCB.00449-17.

ACKNOWLEDGMENTS

We thank T. Kitamura for pMX-puro and Plat-E cells, M. Kaneko for pcDNA3-RNF19B-V5, K. I. Nakayama for E2 expression vectors, H. Takahashi for sharing unpublished data and for discussions, Y. Nagasawa for technical assistance, T. Konishi for secretarial assistance, other laboratory members for discussions, and the Biomedical Research Core of the Tohoku University Graduate School of Medicine for technical support.

This work was funded by KAKENHI grants 25891003 and 17K14955 to T.N., 15K18453 to M.H., 26830064 to R.F., and 26293059, 15K15024, and 17H04035 to K.N. from the Japan Society for the Promotion of Science.

We declare that we have no conflicts of interest.