PMID- 20368827
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20100609
LR  - 20211130
IS  - 2005-9256 (Electronic)
IS  - 1598-2998 (Print)
IS  - 1598-2998 (Linking)
VI  - 36
IP  - 6
DP  - 2004 Dec
TI  - HIF-1alpha: a valid therapeutic target for tumor therapy.
PG  - 343-53
LID - 10.4143/crt.2004.36.6.343 [doi]
AB  - 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-1beta subunit and the highly regulated HIF-1alpha 
      subunits. The stability and activity of HIF-1alpha are regulated by various 
      post-translational modifications, hydroxylation, acetylation, phosphorylation and 
      sumoyaltion. Therefore, HIF-1alpha interacts with several protein factors 
      including PHD, pVHL, ARD-1, SUMO 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, under the hypoxia 
      condition, the HIF-1alpha 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-1alpha is 
      closely associated with a variety of tumors and oncogenic pathways. Hence, the 
      blocking of HIF-1alpha itself or the blocking of HIF-1alpha 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-1alpha stability, the biological functions of HIF-1 and its potential 
      applications for cancer therapies.
FAU - Hong, Soon-Sun
AU  - Hong SS
AD  - Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul 
      National University, Seoul, Korea.
FAU - Lee, Hyunseung
AU  - Lee H
FAU - Kim, Kyu-Won
AU  - Kim KW
LA  - eng
PT  - Journal Article
DEP - 20041231
PL  - Korea (South)
TA  - Cancer Res Treat
JT  - Cancer research and treatment
JID - 101155137
PMC - PMC2843877
OTO - NOTNLM
OT  - ARD1
OT  - Angiogenesis
OT  - Anticancer therapy
OT  - Cell proliferation/survival
OT  - Glucose metabolism
OT  - HIF-1
OT  - Iron metabolism
OT  - PHD
OT  - SUMO
OT  - Transcription factor
OT  - p300/CBP
OT  - pVHL
EDAT- 2004/12/01 00:00
MHDA- 2004/12/01 00:01
PMCR- 2004/12/01
CRDT- 2010/04/07 06:00
PHST- 2010/04/07 06:00 [entrez]
PHST- 2004/12/01 00:00 [pubmed]
PHST- 2004/12/01 00:01 [medline]
PHST- 2004/12/01 00:00 [pmc-release]
AID - 10.4143/crt.2004.36.6.343 [doi]
PST - ppublish
SO  - Cancer Res Treat. 2004 Dec;36(6):343-53. doi: 10.4143/crt.2004.36.6.343. Epub 
      2004 Dec 31.