PMID:21412054

Citation	Culver, C, Melvin, A, Mudie, S and Rocha, S (2011) HIF-1α depletion results in SP1-mediated cell cycle disruption and alters the cellular response to chemotherapeutic drugs. Cell Cycle 10:1249-60
Abstract	Hypoxia inducible factor (HIF) is the major transcription factor involved in the regulation of the cellular response to hypoxia, or low oxygen tensions. Even though HIF-1 function is mostly studied following hypoxic stress, well oxygenated areas of several diseased tissues have detectable levels of this transcription factor. Therefore, it is surprising how little is known about the function of HIF in normoxia. This study seeks to fill this gap. Using transient HIF-1α knockdown, as well as, stable cell lines generated using short hairpin RNAs (shRNA), we have further characterized the role of HIF-1α in normoxia. Our data reveals that knockdown of HIF-1α results in a significant increase in cells in the G1 phase of the cell cycle. We find that HIF-1α depletion increases the protein and mRNA of both p21 and p27. p21 is induced via, at least in part, p53-independent but SP1-dependent mechanisms. Interestingly, HIF-1α knockdown also alters the cellular response to chemotherapeutic agents. These data have important implications in not only for the further understanding of HIF-1α, a major transcription factor, but also for the use of HIF-targeted and combination therapies in cancer treatment.
Links	PubMed PMC3117135
Keywords	Antineoplastic Agents/pharmacology; Apoptosis/drug effects; Autophagy/drug effects; Cell Cycle/drug effects; Cell Hypoxia/drug effects; Cell Hypoxia/genetics; Cell Line, Tumor; Cell Proliferation/drug effects; Cyclin-Dependent Kinase Inhibitor p27/genetics; Cyclin-Dependent Kinase Inhibitor p27/metabolism; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Female; Gene Silencing; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/deficiency; Hypoxia-Inducible Factor 1, alpha Subunit/genetics; Molecular Targeted Therapy; RNA, Messenger/analysis; RNA, Small Interfering/metabolism; Receptors, Immunologic/genetics; Receptors, Immunologic/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transfection; Tumor Markers, Biological/genetics; Tumor Markers, Biological/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:HIF1A		GO:0010508: positive regulation of autophagy	ECO:0000315:		P		Fig 5. When HIF-1α is knockdown, LC3B cleavage, a well characterized marker for autophagy, is reduced in response to doxorubicin and daunorubicin.	complete

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