How is HIF 1a degraded?
HIF-1 is a heterodimeric protein formed by a continuously expressed subunit HIF-1β and an oxygen regulated subunit HIF-1α (Wang et al., 1995a). Under normal oxygen levels, HIF-1α is degraded through the ubiquitin-dependent proteasomal (26S) pathway.
Is HIF-1 alpha a protein?
HIF1A is a basic helix-loop-helix PAS domain containing protein, and is considered as the master transcriptional regulator of cellular and developmental response to hypoxia.
What are the physiological activators of HIF 1a signaling?
The HIF-1α subunit also contains two transactivation domains (TAD), which regulate HIF-1 target genes. CREB binding protein (CBP) and p300, two transcriptional co-activators of HIF-1, interact with the carboxy-terminal transactivation domain (C-TAD) of HIF-1α.
What is HIF stabilization?
In hypoxic conditions, low oxygen leads to HIF-1α stabilization due to the inhibition of proline hydroxylation and subsequent decreases in HIF-1α ubiquitination and degradation. HIF-1α is stabilized and forms, in combination with the HIF-1β subunit, the active HIF-1 complex.
Who discovered HIF-1 alpha?
Discovery of the HIF-1 protein HIF-1 was initially discovered by Semenza and co-workers15 in 1991 during a study conducted on erythropoietin (EPO) gene, a gene responsible for encoding erythropoietin hormone for red blood cells production.
What is the composition of the HIF-1β?
HIF is composed of the constitutive nuclear protein ARNT (arylhydrocarbon receptor nuclear translocator), also termed HIF-1β, and an oxygen-sensitive α-subunit.
What is the function of HIF-1α?
HIF-1α metabolically controls collagen synthesis and modification in chondrocytes Endochondral ossification, an important process in vertebrate bone formation, is highly dependent on correct functioning of growth plate chondrocytes1.
Is HIF1A upregulated by redox sensitivity?
Typically, oxygen-independent pathway regulates protein expression, and oxygen-dependent pathway regulates degradation. In hypoxia-independent ways, HIF1A expression may be upregulated through a redox -sensitive mechanism.
What explains the half-life of HIF-1α after prolonged exposure to hypoxia?
Furthermore, two observations that were published before the characterization of the PHDs are explained by our results: first, the half-life of HIF-1α is shortened by prolonged exposure to hypoxia ( [ 35] and confirmed in the present study). Obviously, the induction of PHD2 and PHD3 would allow faster degradation after long periods of hypoxia.