缺氧诱导因子1α /HIF-1α重组兔单抗

HIF1A

Hypoxia-inducible factor 1-alpha

Interacts with COPS5 subunit of COP9 signalosome complex,leading to the regulation of its stability. Interacts with TSGA10(By similarity). Efficient DNA binding requires heterodimerizationof an alpha and a beta/ARNT subunit. Binds to the TAZ-type 1domains of CREBBP and EP300. Interacts with NCOA1, NCOA2, APEX andHSP90. Interacts with VHL which docks HFA1 to the E3 ubiquitinligase complex for subsequent destruction. Interaction, via the ODDdomain, with the beta domain of VHLL, protects HIF1A fromdestruction by competing against the destructive targetinginitiated by VHL.

Cytoplasm. Nucleus.

Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors.

In normoxia, is hydroxylated on Pro-402 and Pro-564 in theoxygen-dependent degradation domain (ODD) by EGLN1/PHD1 andEGLN2/PHD2. EGLN3/PHD3 has also been shown to hydroxylate Pro-564.The hydroxylated prolines promote interaction with VHL, initiatingrapid ubiquitination and subsequent proteasomal degradation. Underhypoxia, proline hydroxylation is impaired and ubiquitination isattenuated, resulting in stabilization.
In normoxia, is hydroxylated on Asn-803 by HIF1AN, thusabrogating interaction with CREBBP and EP300 and preventingtranscriptional activation.
S-nitrosylation of Cys-800 may be responsible for increasedrecruitment of p300 coactivator necessary for transcriptionalactivity of HIF-1 complex.
Acetylation of Lys-532 by ARD1 increases interaction with VHLand stimulates subsequent proteasomal degradation.
Requires phosphorylation for DNA-binding.

Contains 1 basic helix-loop-helix (bHLH) domain.
Contains 1 PAC (PAS-associated C-terminal) domain.
Contains 2 PAS (PER-ARNT-SIM) domains.

Functions as a master transcriptional regulator of theadaptive response to hypoxia. Under hypoxic conditions activatesthe transcription of over 40 genes, including, erythropoietin,glucose transporters, glycolytic enzymes, vascular endothelialgrowth factor, and other genes whose protein products increaseoxygen delivery or facilitate metabolic adaptation to hypoxia.Plays an essential role in embryonic vascularization, tumorangiogenesis and pathophysiology of ischemic disease. Binds to coreDNA sequence 5'-[AG]CGTG-3' within the hypoxia response element(HRE) of target gene promoters. Activation requires recruitment oftranscriptional coactivators such as CREBPB and EP300. Activity isenhanced by interaction with both, NCOA1 or NCOA2. Interaction withredox regulatory protein APEX seems to activate CTAD andpotentiates activation by NCOA1 and CREBBP.