2008年2月15日 · Oxygen-dependent hydroxylation of hypoxia-inducible factor (HIF)- α subunits by prolyl hydroxylase domain (PHD) proteins signals their polyubiquitination and proteasomal...

2024年4月18日 · We investigated clinically used PHD inhibitors and a new selective PHD inhibitor (IOX5), to stabilize HIF-α in AML cells. PHD inhibition compromises AML in a HIF-1α-dependent manner to...

脯氨酸羟化可让它结合 von Hippel–Lindau 蛋白 (pVHL)，这是一种可靶向 HIF-α 进行蛋白酶体降解的 E3 泛素-连接酶。此外，在不缺氧的条件下，HIF-α 被抑制 HIF-1 (FIH) 的因子天冬酰胺酰羟基化，从而防止 HIF-α 结合共同激活蛋白 p300/CBP。

2019年1月1日 · Cells sense and respond to hypoxia through the activity of the transcription factor HIF (hypoxia-inducible factor) and its regulatory hydroxylases, the prolyl hydroxylase domain enzymes (PHDs). Multiple isoforms of HIFs and PHDs exist, and isoform-selective roles have been identified in the context of the inflammatory environment, which is ...

2008年2月15日 · In the absence of hydroxylation due to hypoxia or PHD inhibition, HIF-1 α translocates to the nucleus, heterodimerizes with HIF-1 β and binds to hypoxia-response elements (HREs) in the...

2020年7月3日 · The stringent expression of the hypoxia inducible factor-1α (HIF-1α) is critical to a variety of pathophysiological conditions. We reveal that, in normoxia, enzymatic action of cystathionine β-synthase (CBS) produces H 2 S, which persulfidates prolyl hydroxylase 2 (PHD2) at residues Cys 21 and Cys 33 (zinc finger motif), augmenting prolyl ...

2021年3月19日 · The hypoxia-inducible factor (HIF-1α) functions as a master regulator of oxygen homeostasis. Oxygen-dependent hydroxylation of HIF-1α is tightly regulated by prolyl hydroxylase domain containing proteins (PHD1, PHD2, and PHD3).

Our preliminary studies have shown that EPO, as a downstream gene of hypoxia inducible factor (HIF), inhibits HIF-1α in a dose-dependent manner in an in-vitro model of hypoxia ischemia. This study is designed to elucidate the primary mediator of EPO-induced HIF-1α inhibition and subsequent cell survival/neuroprotection.

2020年4月30日 · 目前，针对hif-1α和hif-2α的特异性抑制剂正在进行肿瘤适应症的早期临床。 HIF有望成为抗肿瘤药物的潜在靶点。 细胞内HIF表达水平调节示意图

2004年2月29日 · Hypoxia-inducible factor (HIF-1) is an oxygen-dependent transcriptional activator, which plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and one of three subunits (HIF-1alpha, HIF-2alpha or HIF-3alpha).