Hypoxia-inducible factor (HIF
), a basic helix-loop-helix transcription factor composed of an oxygen-sensitive a subunit and a constitutively expressed [beta] subunit, is an important regulatory factor that allows individual cells to adapt to hypoxia (9).
In addition to signal transduction via HIFs
, PHD3 has been shown to stabilize the tight junction protein occludin in IECs by preventing its interaction with the E3 ligase Itch in a hydroxylase-independent manner .
also lead to downregulation of tryptophanyl-tRNA synthetase (TrpRS) which has been studied in both colorectal and pancreatic cancers for its significance in prognosis .
 reported that aquaporins (AQP), proteins that control water secretion and play an important role during the first step of saliva synthesis, were regulated by HIF
, suggesting a possible mechanism by which hypoxia could decrease the salivary flow rate.
In addition to producing pseudohypoxia by stabilizing HIFs
, a feature shared by the other oncometabolites, fumarate also promotes a pseudohypoxic milieu by noncanonical activation of nuclear factor -B signaling, leading to increased transcription of HIF-1 (34).
 To survive under such reduced oxygen concentration, tumor cell adapts some transcriptional expression where HIF
is a key transcriptional factor.
In hypoxic environments, limited amount of oxygen leads to metabolic switches in both normal and malignant cells by HIFs
. Paradoxically, recent studies have shown that CSC exhibit high HIF
activity in normoxic environments and that HIF
activity is critical in the maintenance of CSC as well as in the differentiation .
"One of the top leaders of Ahrar al-Sham terrorist group, Yamen Kan'an also known as Abu Hifs
, was killed in the car carrying him along with some of his comrades on a road near the city of al-Nasiriya in Eastern Qalamoun," the military source on the ground said.
The normal response to hypoxia is mediated by hypoxia response genes, which include hypoxia inducible factors (HIFs
), for example, HIF-1[alpha] and HIF-2[alpha].
The adaptation of cells to reduced oxygen tensions is largely coordinated by hypoxia-inducible factors (HIFs
) which have come into the focus of immunological research during the last ten years.
Hypoxia causes stabilization and activation of proteins called hypoxia-inducible factors (HIFs
), which regulate multiple pathways that control cell survival, proliferation, and metabolism.
The rela-tive improvements in both iron and the saturation of its carrier (TSAT) may be explained by the role played by hypoxia inducible factors (HIFs