@article{1dc5bd7ee6454fe0955092986e04db95,
title = "Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor",
abstract = "Direct interactions between pro- and anti-apoptotic BCL-2 family members form the basis of cell death decision-making at the outer mitochondrial membrane (OMM). Here we report that three anti-apoptotic BCL-2 proteins (MCL-1, BCL-2 and BCL-XL) found untethered from the OMM function as transcriptional regulators of a prosurvival and growth program. Anti-apoptotic BCL-2 proteins engage a BCL-2 homology (BH) domain sequence found in SUFU (suppressor of fused), a tumour suppressor and antagonist of the GLI DNA-binding proteins. BCL-2 proteins directly promote SUFU turnover, inhibit SUFU-GLI interaction, and induce the expression of the GLI target genes BCL-2, MCL-1 and BCL-XL. Anti-apoptotic BCL-2 protein/SUFU feedforward signalling promotes cancer cell survival and growth, and can be disabled with BH3 mimetics - small molecules that target anti-apoptotic BCL-2 proteins. Our findings delineate a chemical strategy for countering drug resistance in GLI-associated tumours and reveal unanticipated functions for BCL-2 proteins as transcriptional regulators.",
author = "Xiaofeng Wu and Zhang, {Li Shu} and Jason Toombs and Kuo, {Yi Chun} and Piazza, {John Tyler} and Rubina Tuladhar and Quinn Barrett and Fan, {Chih Wei} and Xuewu Zhang and Walensky, {Loren D.} and Marcel Kool and Cheng, {Steven Y.} and Rolf Brekken and Opferman, {Joseph T.} and Green, {Douglas R.} and Tudor Moldoveanu and Lawrence Lum",
note = "Funding Information: We thank C. Chen, R. Toftg{\aa}rd, X. Wang, S. Skypek, M. P. Scott, and J. K. Chen for reagents. This work was supported in part by the Welch Foundation (I-1665, L.L.) and CPRIT (RP130212, L.L.). Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01CA168761 (L.L.), R01CA196851 (L.L.) and P50-CA70907 (Minna). Q.B. was supported by a T32 training grant (5T32CA124334). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S.Y.C. was supported by the National Basic Research Program of China (2012CB945003). Publisher Copyright: {\textcopyright} 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2017",
month = sep,
day = "29",
doi = "10.1038/ncb3616",
language = "English (US)",
volume = "19",
pages = "1226--1236",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "10",
}