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Four-and-a-Half LIM Domain Proteins Inhibit Transactivation by Hypoxia-inducible Factor 1
Four-and-a-Half LIM Domain Proteins Inhibit Transactivation by Hypoxia-inducible Factor 1
- Source :
- Journal of Biological Chemistry. 287:6139-6149
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that promotes angiogenesis, metabolic reprogramming, and other critical aspects of cancer biology. The four-and-a-half LIM domain (FHL) proteins are a family of LIM domain-only proteins implicated in transcriptional regulation and suppression of tumor growth. Here we describe functional interactions between the FHL proteins and HIF-1. FHL1-3 inhibit HIF-1 transcriptional activity and HIF-1α transactivation domain function by oxygen-independent mechanisms. FHL2 directly interacts with HIF-1α to repress transcriptional activity. FHL1 binds to the p300/CBP co-activators and disrupts binding with HIF-1α. FHL3 does not bind to HIF-1α or p300, indicating that it regulates transactivation by a novel molecular mechanism. Expression of the FHL proteins increased upon HIF-1α induction, suggesting the existence of a feedback loop. These results identify FHL proteins as negative regulators of HIF-1 activity, which may provide a mechanism by which they suppress tumor growth.
- Subjects :
- Transcriptional Activation
Carcinoma, Hepatocellular
LIM-Homeodomain Proteins
Muscle Proteins
Uterine Cervical Neoplasms
P300-CBP Transcription Factors
Biology
Biochemistry
Transactivation
Transcriptional regulation
Humans
p300-CBP Transcription Factors
Gene Regulation
Molecular Biology
Transcription factor
LIM domain
Feedback, Physiological
fungi
Intracellular Signaling Peptides and Proteins
food and beverages
FHL3
Cell Biology
LIM Domain Proteins
Hypoxia-Inducible Factor 1, alpha Subunit
Cell Hypoxia
Kidney Neoplasms
FHL1
Protein Structure, Tertiary
FHL2
Cell biology
Gene Expression Regulation, Neoplastic
HEK293 Cells
Female
HeLa Cells
Transcription Factors
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 287
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....2e68665816fe9473d679e4cb16aecf65
- Full Text :
- https://doi.org/10.1074/jbc.m111.278630