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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2004.1
- 수록면
- 1 - 12 (12page)
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Hypoxia-inducible factor (HIF-1) is an oxygen-dependent transcriptional activator, which plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and one of three subunits (HIF-1alpha, HIF-2alpha or HIF-3alpha). The stability and activity of HIF-1alpha are regulated by various post-translational modifications, hydroxylation, acetylation, and phosphorylation. Therefore, HIF-1alpha interacts with several protein factors including PHD, pVHL, ARD-1, and p300/CBP. Under normoxia, the HIF-1alpha subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)- mediated ubiquitin-proteasome pathway. The association of pVHL and HIF-1alpha under normoxic conditions is triggered by the hydroxylation of prolines and the acetylation of lysine within a polypeptide segment known as the oxygen-dependent degradation (ODD) domain. On the contrary, in the hypoxia condition, HIF-1alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Eventually, HIF-1 acts as a master regulator of numerous hypoxia-inducible genes under hypoxic conditions. The target genes of HIF-1 are especially related to angiogenesis, cell proliferation/survival, and glucose/iron metabolism. Moreover, it was reported that the activation of HIF-1alpha is closely associated with a variety of tumors and oncogenic pathways. Hence, the blocking of HIF-1a itself or HIF-1alpha interacting proteins inhibit tumor growth. Based on these findings, HIF-1 can be a prime target for anticancer therapies. This review summarizes the molecular mechanism of HIF-1a stability, the biological functions of HIF-1 and its potential applications of cancer therapies.
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참고문헌 (28)
참고문헌 신청
/ / elegans EGL-9 and mammalian homologs define afamily of dioxygenases that regulate HIF by prolyl hydroxylation : 43 ~ 54
/ 1996 / An essential rolefor p300/CBP in the cellular response to hypoxia 93 : 12969 ~ 73
/ 1996 / Oxygen sensing and molecular adaptationto hypoxia 76 : 839 ~ 85
/ 1997 / Characterization ofthe alpha1B-adrenergic receptor gene promoter region andhypoxia regulatory elements in vascular smooth muscle 94 : 9487 ~ 92
/ 1997 / Reciprocal positive
/ 1996 / An essential rolefor p300/CBP in the cellular response to hypoxia 93 : 12969 ~ 73
/ 1996 / Oxygen sensing and molecular adaptationto hypoxia 76 : 839 ~ 85
/ 1997 / Characterization ofthe alpha1B-adrenergic receptor gene promoter region andhypoxia regulatory elements in vascular smooth muscle 94 : 9487 ~ 92
/ 1997 / Reciprocal positive
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STAT3 inhibits the degradation of HIF-1α by pVHL-mediated ubiquitination
Experimental and Molecular Medicine
2008 .01
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Regulation of glucose metabolism-related genes and VEGF by HIF-1α and HIF-1β, but not HIF-2α, in gastric cancer
Experimental and Molecular Medicine
2009 .01
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2015 .01
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Hypoxia and angiogenesis: regulation of hypoxia-inducible factors via novel binding factors
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2009 .01
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Hypoxia signaling in human diseases and therapeutic targets
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Experimental and Molecular Medicine
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Functional Role of a Conserved Sequence Motif in the Oxygen-dependent Degradation Domain of Hypoxia-inducible Factor 1α in the Recognition of p53
Genomics & informatics
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Association of DNA-dependent protein kinase w ith hypoxia inducible factor-1 and its im plication in resistance to anticancer drugs in hypoxic tumor cells
Experimental and Molecular Medicine
2004 .01
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Constitutive stabilization of hypoxia-inducible factor alpha selectively promotes the self-renewal of mesenchymal progenitors and maintains mesenchymal stromal cells in an undifferentiated state
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2013 .01
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Experimental and Molecular Medicine
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Phospholipase D activates HIF-1-VEGF pathway via phosphatidic acid
Experimental and Molecular Medicine
2014 .01
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Effects of echinomycin on endothelin-2 expression and ovulation in immature rats primed with gonadotropins
Experimental and Molecular Medicine
2012 .01
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Tissue microarray를 이용한 여러 암에서의 thymosin β4, vascular endothelial growth factor, 및 hypoxia-inducible factor-1α 발현양상 연구
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The pleckstrin homology domain of phospholipase D1 accelerates EGFR endocytosis by increasing the expression of the Rab5 effector, rabaptin-5
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2015 .01
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Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis
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저산소증 상태에서 B16F10 피부암 세포에 EGCG를 처리하였을 때의 apoptosis 효과
생명과학회지
2011 .02
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