CDK7 Regulates the Mitochondrial Localization of a Tail-Anchored Proapoptotic Protein, Hid
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 protei...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2013-12-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713006979 |
id |
doaj-8d36d89edda042f3bdc4be5df99efa94 |
---|---|
record_format |
Article |
spelling |
doaj-8d36d89edda042f3bdc4be5df99efa942020-11-24T22:11:21ZengElsevierCell Reports2211-12472013-12-01561481148810.1016/j.celrep.2013.11.030CDK7 Regulates the Mitochondrial Localization of a Tail-Anchored Proapoptotic Protein, HidJun Morishita0Min-Ji Kang1Kevin Fidelin2Hyung Don Ryoo3Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USADepartment of Cell Biology, New York University School of Medicine, New York, NY 10016, USADepartment of Cell Biology, New York University School of Medicine, New York, NY 10016, USADepartment of Cell Biology, New York University School of Medicine, New York, NY 10016, USA 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. http://www.sciencedirect.com/science/article/pii/S2211124713006979 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jun Morishita Min-Ji Kang Kevin Fidelin Hyung Don Ryoo |
spellingShingle |
Jun Morishita Min-Ji Kang Kevin Fidelin Hyung Don Ryoo CDK7 Regulates the Mitochondrial Localization of a Tail-Anchored Proapoptotic Protein, Hid Cell Reports |
author_facet |
Jun Morishita Min-Ji Kang Kevin Fidelin Hyung Don Ryoo |
author_sort |
Jun Morishita |
title |
CDK7 Regulates the Mitochondrial Localization of a Tail-Anchored Proapoptotic Protein, Hid |
title_short |
CDK7 Regulates the Mitochondrial Localization of a Tail-Anchored Proapoptotic Protein, Hid |
title_full |
CDK7 Regulates the Mitochondrial Localization of a Tail-Anchored Proapoptotic Protein, Hid |
title_fullStr |
CDK7 Regulates the Mitochondrial Localization of a Tail-Anchored Proapoptotic Protein, Hid |
title_full_unstemmed |
CDK7 Regulates the Mitochondrial Localization of a Tail-Anchored Proapoptotic Protein, Hid |
title_sort |
cdk7 regulates the mitochondrial localization of a tail-anchored proapoptotic protein, hid |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-12-01 |
description |
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.
|
url |
http://www.sciencedirect.com/science/article/pii/S2211124713006979 |
work_keys_str_mv |
AT junmorishita cdk7regulatesthemitochondriallocalizationofatailanchoredproapoptoticproteinhid AT minjikang cdk7regulatesthemitochondriallocalizationofatailanchoredproapoptoticproteinhid AT kevinfidelin cdk7regulatesthemitochondriallocalizationofatailanchoredproapoptoticproteinhid AT hyungdonryoo cdk7regulatesthemitochondriallocalizationofatailanchoredproapoptoticproteinhid |
_version_ |
1725806085251530752 |