NDLI: A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation

Content Provider	PubMed Central
Author	Lin, Xiaoyu David, Caroline A. Donnelly, Jennifer B. Michaelides, Mike Chandel, Navdeep S. Huang, Xiaoli Warrior, Usha Weinberg, Frank Tormos, Kathryn V. Fesik, Stephen W. Shen, Yu
Copyright Year	2008
Abstract	Hypoxia-inducible factor-1 (HIF-1) plays an essential role in tumor development and progression by regulating genes that are vital for proliferation, glycolysis, angiogenesis, and metastasis. To identify strategies of targeting the HIF-1 pathway, we screened a siRNA library against the entire druggable genome and a small-molecule library consisting of 691,200 compounds using a HIF-1 reporter cell line. Although the siRNA library screen failed to reveal any druggable targets, the small-molecule library screen identified a class of alkyliminophenylacetate compounds that inhibit hypoxia-induced HIF-1 reporter activity at single-digit nanomolar concentrations. These compounds were found to inhibit hypoxia but not deferoxamine-induced HIF-1α protein stabilization. Further analysis indicated that the alkyliminophenylacetate compounds likely inhibit the HIF-1 pathway through blocking the hypoxia-induced mitochondrial reactive oxygen species (ROS) production. Strikingly, all of the nonalkyliminophenylacetate HIF-1 inhibitors identified from the small-molecule library screen were also found to target mitochondria like the alkyliminophenylacetate compounds. The exclusive enrichment of mitochondria inhibitors from a library of >600,000 diverse compounds by using the HIF-1 reporter assay highlights the essential role of mitochondria in HIF-1 regulation. These results also suggest that targeting mitochondrial ROS production might be a highly effective way of blocking HIF-1 activity in tumors.
Related Links	http://dx.doi.org/10.1073/pnas.0706585104
Starting Page	174
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	105
Language	English
Publisher	National Academy of Sciences
Publisher Date	2008-01-08
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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

The essential role of Cited2, a negative regulator for HIF-1α, in heart development and neurulation

Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate

A genome-wide screen in Saccharomyces cerevisiae reveals a critical role for the mitochondria in the toxicity of a trichothecene mycotoxin

Novel functions of the phosphatidylinositol metabolic pathway discovered by a chemical genomics screen with wortmannin

The Role of Factor Inhibiting HIF (FIH-1) in Inhibiting HIF-1 Transcriptional Activity in Glioblastoma Multiforme

Insights into Illicit Transport and Transcription Regulation from a Chemical-Genomic Screen in Escherichia coli

Regulation of a rat VL30 element in human breast cancer cells in hypoxia and anoxia: role of HIF-1

Kinome-Wide Functional Genomics Screen Reveals a Novel Mechanism of TNFα-Induced Nuclear Accumulation of the HIF-1α Transcription Factor in Cancer Cells

Role of Nonohmicity in the Regulation of Electron Transport in Plant Mitochondria 1

A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation

Similar Documents

The essential role of Cited2, a negative regulator for HIF-1α, in heart development and neurulation

Haploinsufficiency screen highlights two distinct groups of ribosomal protein genes essential for embryonic stem cell fate

A genome-wide screen in Saccharomyces cerevisiae reveals a critical role for the mitochondria in the toxicity of a trichothecene mycotoxin

Novel functions of the phosphatidylinositol metabolic pathway discovered by a chemical genomics screen with wortmannin

The Role of Factor Inhibiting HIF (FIH-1) in Inhibiting HIF-1 Transcriptional Activity in Glioblastoma Multiforme

Insights into Illicit Transport and Transcription Regulation from a Chemical-Genomic Screen in Escherichia coli

Regulation of a rat VL30 element in human breast cancer cells in hypoxia and anoxia: role of HIF-1

Kinome-Wide Functional Genomics Screen Reveals a Novel Mechanism of TNFα-Induced Nuclear Accumulation of the HIF-1α Transcription Factor in Cancer Cells

Role of Nonohmicity in the Regulation of Electron Transport in Plant Mitochondria 1

A chemical genomics screen highlights the essential role of mitochondria in HIF-1 regulation