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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2004.1
- 수록면
- 343 - 353 (11page)
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초록· 키워드
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Hypoxia plays a major role in the induction of angiogenesis during tumor development. One mechanism by which tumor cells respond to a reduced oxygen level is via the activation of hypoxia-inducible factor-1 (HIF-1).
HIF-1 is an oxygen-dependent transcriptional activator that plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1β subunit and the highly regulated HIF-1α subunits. The stability and activity of HIF-1α are regulated by various post-translational modifications, hydroxylation, acetylation, phosphorylation and sumoyaltion.
Therefore, HIF-1α interacts with several protein factors including PHD, pVHL, ARD-1, SUMO and p300/ CBP.
Under normoxia, the HIF-1α subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)-mediated ubiquitin/proteasome pathway. The association of pVHL and HIF-1α 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, under the hypoxia condition, the HIF-1α subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Under hypoxic conditions, HIF-1 eventually acts as a master regulator of numerous hypoxia-inducible genes.
The target genes of HIF-1 are especially related to angiogenesis, cell proliferation and survival, and to glucose and iron metabolism. Moreover, it was reported that the activation of HIF-1α is closely associated with a variety of tumors and oncogenic pathways. Hence, the blocking of HIF-1α itself or the blocking of HIF-1α interacting proteins inhibits tumor growth. Based on these findings, HIF-1 can be a prime target for anticancer therapies. Therefore, this review summarizes the molecular mechanism of HIF-1α stability, the biological functions of HIF-1 and its potential applications for cancer therapies.
#ARD1
#Angiogenesis
#Anticancer therapy
#Cell proliferation/survival
#Glucose metabolism
#HIF-1
#Iron metabolism
#PHD
#SUMO
#pVHL
#p300/CBP
#Transcription factor
#ARD1
#Angiogenesis
#Anticancer therapy
#Cell proliferation/survival
#Glucose metabolism
#HIF-1
#Iron metabolism
#PHD
#SUMO
#pVHL
#p300/CBP
#Transcription factor
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등록된 정보가 없습니다.
참고문헌 (30)
참고문헌 신청
[학술지(정기간
/ 1995 / Effect of protein kinaseand phosphatase inhibitors on expression of HIF-1 216 : 669 ~ 75
/ 1996 / and transactivation properties of HIF-1α : 17771 ~ 8
/ 1997 / a transcription factor selectively expressed in endothelialcells : 72 ~ 82
/ 1999 / Early stages of multistephepatocarcinogenesis 22 : 172 ~ 8
/ 1995 / Effect of protein kinaseand phosphatase inhibitors on expression of HIF-1 216 : 669 ~ 75
/ 1996 / and transactivation properties of HIF-1α : 17771 ~ 8
/ 1997 / a transcription factor selectively expressed in endothelialcells : 72 ~ 82
/ 1999 / Early stages of multistephepatocarcinogenesis 22 : 172 ~ 8
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