Identifiers
HUGO:ARNT HGNC:700
aryl hydrocarbon receptor nuclear translocator
HUGO:ARNT, HGNC:700, ENTREZ:405, GENECARDS:GC01M150782, UNIPROT:P27540
HUGO:ARNT HGNC:700 ENTREZ:405 UNIPROT:P27540
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / SENESCENCE
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / GLUCOSE_METABOLISM
Regulated Cell Death / RCD_GENES
References
PMID:8756616
http://www.omicsonline.org/1948-5956/JCST-03-035.php
HIF-1 is the Commander of Gateways to Cancer
PMID:16887934
PMID:9159130
HIF-1B (ARNT) is constitutively expressed and itsmRNA and protein are maintained at constant levels regardless of oxygen availability
PMID:9278421
HIF-1A protein has a short half-life (t1/2 = 5 min) and is highly regulated by oxygen
PMID:9746763
The transcription and synthesis of HIF-1B are constitutive and seem not to be affected by oxygen.
PMID:7539918
In normoxia, the HIF-1A proteins are rapidly degraded, resulting in essentially no detectable HIF-1A protein.
PMID:8943284
During hypoxia, HIF-1A becomes stabilized and translocates from the cytoplasm to the nucleus, where it dimerizes with HIF-1B and the HIF complex formed becomes transcriptionally active
PMID:1823643
The activated HIF complex then associates with HREs in the regulatory regions of target genes and binds the transcriptional coactivators to induce gene expression.
PMID:15451019
Tight regulation of the stability and subsequent transactivational function of HIF-1A is chiefly controlled by its post-translation modifications, such as hydroxylation, ubiquitination, acetylation, and phosphorylation
The modification of HIF-1A occurs within several domains.
PMID:10403805
PMID:11566883
PMID:12829734
In normoxia, hydroxylation of 2 proline residues and acetylation of a lysine residue in its ODDD promote interaction of HIF-1A with the von Hippel-Lindau (pVHL) ubiquitin E3 ligase complex (Srinivas et al., 1999; Masson et al., 2001).
PMID:12080085
pVHL complex tags HIF-1A with ubiquitin and thereby marks it for degradation by the 26S proteasome.
In addition, hydroxylation of an asparagine residue in the C-TAD inhibits the association of HIF-1A with CBP/p300 and thus inhibits its transcriptional activity (Lando et al., 2002a).
synonym:HIF1beta
References
em_emtc_emtc_re406( EMT Senescence ):
PMID:13130303
Regulation of HIF-1a protein synthesis
MNK phosphorylates eIF-4E and stimulates its activity directly.
Active eIF-4E increases the rate of HIF1A-mRNA translation into HIF1A protein.
PMID:16887934
PMID:9159130
HIF-1B (ARNT) is constitutively expressed and itsmRNA and protein are maintained at constant levels regardless of oxygen availability
PMID:9278421
HIF-1A protein has a short half-life (t1/2 = 5 min) and is highly regulated by oxygen
PMID:9746763
The transcription and synthesis of HIF-1B are constitutive and seem not to be affected by oxygen.
PMID:7539918
In normoxia, the HIF-1A proteins are rapidly degraded, resulting in essentially no detectable HIF-1A protein.
PMID:8943284
During hypoxia, HIF-1A becomes stabilized and translocates from the cytoplasm to the nucleus, where it dimerizes with HIF-1B and the HIF complex formed becomes transcriptionally active
PMID:1823643
The activated HIF complex then associates with HREs in the regulatory regions of target genes and binds the transcriptional coactivators to induce gene expression.
PMID:15451019
Tight regulation of the stability and subsequent transactivational function of HIF-1A is chiefly controlled by its post-translation modifications, such as hydroxylation, ubiquitination, acetylation, and phosphorylation
The modification of HIF-1A occurs within several domains.
PMID:10403805
PMID:11566883
PMID:12829734
In normoxia, hydroxylation of 2 proline residues and acetylation of a lysine residue in its ODDD promote interaction of HIF-1A with the von Hippel-Lindau (pVHL) ubiquitin E3 ligase complex (Srinivas et al., 1999; Masson et al., 2001).
PMID:12080085
pVHL complex tags HIF-1A with ubiquitin and thereby marks it for degradation by the 26S proteasome.
In addition, hydroxylation of an asparagine residue in the C-TAD inhibits the association of HIF-1A with CBP/p300 and thus inhibits its transcriptional activity (Lando et al., 2002a).
em_emtc_emtc_re1242( EMT Senescence ):
PMID:16716598
HIF-1 plays critical roles in angiogenesis during embryonic development and disease pathogenesis
Maps_Modules
HMC:RESISTING_CELL_DEATH
HMC:DEREGULATING_CELLULAR_ENERGETICS
Regulated Cell Death / GLUCOSE_METABOLISM
Regulated Cell Death / RCD_GENES
References
rc_re1200( Regulated Cell Death ):
PMID:20308559
bioinformatic prediction
in HCT116, expression of MIR107 precursor decreases ARNT protein abundance
in HCT116, in Hela, in SW480, RNA antisens to MIR107 increases ARNT protein abundance
+ luciferase reporter assay using the 3'UTR of ARNT
in HCT116, knockdown of endogenous miR-107 increased desferrioxamine(hypoxia mimick)-induced VEGF levels, which is rescued by a expression of ARNT lacking its 3'UTR.
in HCT116, pre-miR-107 decreases the ability of HCT116 cells to stimulate endothelial proliferation upon hypoxia (MMT assay)
+ p300*@Nucleus → HIF1A:HIF1B*:p300*@Nucleus
→ Angiogenesis@Nucleus
→ HIF1B*@Cytosol
+ HIF1B*@Cytosol → em_emtc_emtc_s1611
→ HIF1B*@Nucleus
+ HIF1A:HIF1B*@Nucleus → rc_s2451
+ O_sub_2_endsub_@Nucleus + 2-oxoglutarate@Nucleus → rc_s5678 + CO_sub_2_endsub_@Nucleus + succinate@Nucleus
+ HIF1B*@Nucleus → HIF1A:HIF1B*@Nucleus
+ CITED2@Nucleus → rc_s5675
→ degraded
→ rVEGFA@Nucleus