NDLI: Proto-oncogene CT10-regulated kinase (CRK) is a pro-apoptotic transducer of endoplasmic reticulum stress

Please wait, while we are loading the content...

Proto-oncogene CT10-regulated kinase (CRK) is a pro-apoptotic transducer of endoplasmic reticulum stress

Content Provider	PubMed Central
Author	Austgen, Kathryn Johnson, Emily T. Park, Tae-ju Curran, Tom Oakes, Scott A.
Abstract	Excessive demands on the protein folding capacity of the endoplasmic reticulum (ER) cause irremediable ER stress and contribute to cell loss in a number of cell degenerative diseases, including type 2 diabetes and neurodegeneration 1,2 . The signals communicating catastrophic ER damage to the mitochondrial apoptotic machinery remain poorly understood 3-6 . We used a biochemical approach to purify a cytosolic activity induced by ER stress that causes release of cytochrome c from isolated mitochondria. We discovered that the principal component of the purified pro-apoptotic activity is proto-oncogene CT10-regulated kinase (CRK), an adaptor protein with no known catalytic activity 7 . Crk -/- cells are strongly resistant to ER stress-induced apoptosis. Moreover, CRK is cleaved in response to ER stress to generate an N-terminal ~14kD fragment with greatly enhanced cytotoxic potential. We identified a putative BCL2 homology-3 (BH3) domain within this N-terminal CRK fragment, which sensitizes isolated mitochondria to cytochrome c release and when mutated significantly reduces CRK's apoptotic activity in vivo. Together these results identify CRK as a pro-apoptotic protein that signals irremediable ER stress to the mitochondrial execution machinery.
Related Links	http://dx.doi.org/10.1038/ncb2395
Ending Page	92
Page Count	6
Starting Page	87
File Format	PDF
ISSN	14657392
e-ISSN	14764679
Journal	Nature cell biology
Issue Number	1
Volume Number	14
Language	English
Publisher Date	2011-12-01
Access Restriction	Open
Subject Keyword	Cell Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Cdk5 and Mekk1 mediate a Pro-Apoptotic Signaling Response to Endoplasmic Reticulum Stress in a Drosophila Model of Autosomal Dominant Retinitis Pigmentosa

Two In-and-out Modulation Strategies for Endoplasmic Reticulum Stress-linked Gene Expression of Pro-apoptotic Macrophage-inhibitory Cytokine 1

Late Phase of the Endoplasmic Reticulum Stress Response Pathway Is Regulated by Hog1 MAP Kinase*

Glioblastoma Proto-Oncogene SEC61γ Is Required for Tumor Cell Survival and Response to Endoplasmic Reticulum Stress

The Endoplasmic Reticulum Stress Transducer OASIS Is involved in the Terminal Differentiation of Goblet Cells in the Large Intestine

Gossypol Increases Expression of the Pro-apoptotic BH3-only Protein NOXA through a Novel Mechanism Involving Phospholipase A2, Cytoplasmic Calcium, and Endoplasmic Reticulum Stress

Rottlerin induces pro-apoptotic endoplasmic reticulum stress through the protein kinase C-δ-independent pathway in human colon cancer cells

Resveratrol triggers the pro-apoptotic endoplasmic reticulum stress response and represses the pro-survival XBP1 signaling in human multiple myeloma cells

Two In-and-out Modulation Strategies for Endoplasmic Reticulum Stress-linked Gene Expression of Pro-apoptotic Macrophage-inhibitory Cytokine 1*

Proto-oncogene CT10-regulated kinase (CRK) is a pro-apoptotic transducer of endoplasmic reticulum stress

Similar Documents

Cdk5 and Mekk1 mediate a Pro-Apoptotic Signaling Response to Endoplasmic Reticulum Stress in a Drosophila Model of Autosomal Dominant Retinitis Pigmentosa

Two In-and-out Modulation Strategies for Endoplasmic Reticulum Stress-linked Gene Expression of Pro-apoptotic Macrophage-inhibitory Cytokine 1

Late Phase of the Endoplasmic Reticulum Stress Response Pathway Is Regulated by Hog1 MAP Kinase*

Glioblastoma Proto-Oncogene SEC61γ Is Required for Tumor Cell Survival and Response to Endoplasmic Reticulum Stress

The Endoplasmic Reticulum Stress Transducer OASIS Is involved in the Terminal Differentiation of Goblet Cells in the Large Intestine

Gossypol Increases Expression of the Pro-apoptotic BH3-only Protein NOXA through a Novel Mechanism Involving Phospholipase A2, Cytoplasmic Calcium, and Endoplasmic Reticulum Stress

Rottlerin induces pro-apoptotic endoplasmic reticulum stress through the protein kinase C-δ-independent pathway in human colon cancer cells

Resveratrol triggers the pro-apoptotic endoplasmic reticulum stress response and represses the pro-survival XBP1 signaling in human multiple myeloma cells

Two In-and-out Modulation Strategies for Endoplasmic Reticulum Stress-linked Gene Expression of Pro-apoptotic Macrophage-inhibitory Cytokine 1*

Proto-oncogene CT10-regulated kinase (CRK) is a pro-apoptotic transducer of endoplasmic reticulum stress