Progress on hypoxia-inducible factor-3: Its structure, gene regulation and biological function (Review).
Hypoxia inducible factors (HIFs) are transcription factors, which are commonly expressed in mammals, including humans. The HIFs consist of hypoxia-regulated α and oxygen-insensitive β subunits, and are key regulators of gene expression during hypoxia in normal and solid tumor tissues. Three members of the HIF family, HIF-1α, HIF-2α, and HIF-3α, are currently known. HIF-3α differs from HIF-1α and HIF-2α in protein structure and regulation of gene expression. For a long time, HIF-3α was considered as a negative mediator of HIF-regulated genes. HIF-3 has a transcriptional regulatory function, which negatively affects gene expression by competing with HIF-1α and HIF-2α in binding to transcriptional elements in target genes during hypoxia. Previously, certain target genes of HIF-3α have been identified, confirming the role of HIF-3α as a transcription factor. In this review, the protein structure, gene regulation and biological function of HIF-3 are discussed based on the literature.
Department of General Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
Sheng-Li
SL
Yang
Department of General Surgery, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
Chao
C
Wu
Department of Medicine and Division of Digestion Disease, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, P.R. China.
Zhi-Fan
ZF
Xiong
Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Xiefan
X
Fang
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015687:Cell Hypoxia / Q000235:genetics; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016366:Open Reading Frames; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins; D020218:Response Elements; D015398:Signal Transduction; D014158:Transcription, Genetic; D000099162:Endothelial PAS Domain-Containing Protein 1
D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012097:Repressor Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C116973:HIF3A protein, human