CDK7 regulates the mitochondrial localization of a tail-anchored proapoptotic protein, Hid

Cell Reports
Jun MorishitaHyung Don Ryoo

Abstract

The mitochondrial outer membrane is a major site of apoptosis regulation across phyla. Human and C. elegans Bcl-2 family proteins and Drosophila Hid require the C-terminal tail-anchored (TA) sequence in order to insert into the mitochondrial membrane, but it remains unclear whether cytosolic proteins actively regulate the mitochondrial localization of these proteins. Here, we report that the cdk7 complex regulates the mitochondrial localization of Hid and its ability to induce apoptosis. We identified cdk7 through an in vivo RNAi screen of genes required for cell death. Although CDK7 is best known for its role in transcription and cell-cycle progression, a hypomorphic cdk7 mutant suppressed apoptosis without impairing these other known functions. In this cdk7 mutant background, Hid failed to localize to the mitochondria and failed to bind to recombinant inhibitors of apoptosis (IAPs). These findings indicate that apoptosis is promoted by a newly identified function of CDK7, which couples the mitochondrial localization and IAP binding of Hid.

References

Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·N J ColleyC S Zuker
Apr 29, 1994·Science·K WhiteH Steller
Feb 9, 1996·Science·K WhiteH Steller
Jul 15, 1996·Genes & Development·P ChenJ M Abrams
Feb 28, 1998·Genes & Development·S LarochelleB Suter
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·W N HainingH Steller
May 22, 2002·Nature Cell Biology·Hyung Don RyooHermann Steller
Jul 3, 2002·The EMBO Journal·Cristina ClaveríaMiguel Torres
Aug 15, 2003·The Journal of Biological Chemistry·Michael R OlsonSally Kornbluth
Nov 11, 2005·Journal of Cell Science·Robert P Fisher
Dec 16, 2006·The EMBO Journal·Hyung Don RyooHermann Steller
Mar 30, 2007·Proceedings of the National Academy of Sciences of the United States of America·Elenita I KaninAseem Z Ansari
May 10, 2007·Developmental Cell·Eltyeb AbdelwahidKristin White
Jul 17, 2007·Current Opinion in Cell Biology·Nica BorgeseSara Colombo
Sep 15, 2010·The Journal of Cell Biology·Cristinel SanduHermann Steller
Sep 18, 2010·Current Opinion in Cell Biology·Hyung Don Ryoo, Eric H Baehrecke
Nov 17, 2011·Nature Reviews. Molecular Cell Biology·Ramanujan S Hegde, Robert J Keenan

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Citations

Dec 19, 2015·Apoptosis : an International Journal on Programmed Cell Death·Amandine ClavierIsabelle Guénal
Dec 3, 2014·Current Opinion in Cell Biology·Isabel C Lopez-Mejia, Lluis Fajas
Aug 7, 2018·PLoS Genetics·Rebecca A S Palu, Clement Y Chow
Apr 25, 2020·International Journal of Molecular Sciences·Benshui ShuGuohua Zhong
Jul 26, 2015·Journal of Cell Science·Amandine ClavierIsabelle Guénal
Sep 26, 2021·Cell Death Discovery·Bin LiuMeixiao Zhan

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