P4HA1

Official Full Name

prolyl 4-hydroxylase subunit alpha 1

Organism

Homo sapiens

GeneID

5033

Background

This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Synonyms

P4HA;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

P4HA1 working as a new regulator of breast cancer in the HIF-1 pathway

Hypoxia-Inducible Factor (HIF)-1, a transcription factor, makes good contributions in response to low oxygen concentrations, or hypoxia. However, activation of the HIF-1 pathway not only matters in normal tissue development and function, but also has involvement in disease progression, like cancer. Rapid proliferation of cancer cell in solid tumors would consume more oxygen and nutrients in comparison with normal tissue, and it can cause oxygen tensions, which is well established to be the inducer of the aberrant activation of the HIF-1 pathway in solid tumor tissues. Breast cancer is recognized as a heterogeneous disease and can be classified into ER/PR and Her2 expression-based subtypes, which included by luminal, Her2 positive, and triple negative (TNBC). And hyperactivation of HIF-1 pathway in TNBCs in comparison to other subtypes may suggest that oxygen-independent pathways are involved in HIF-1 regulated TNBC progression, although it may not have been well-characterized. Collagen proly 4 hydroxylase 1 (P4H1) has been demonstrated to be capable of regulating HIF-1α expression at protein level by re-modulating of α-ketoglutarate (α-KG）and succinate levels. This link between collagen hydroxylation and the HIF-1 pathway presented a novel mechanism of HIF-1 regulated mechanism in TNBC.

P4HA1 acts as a target of microRNA-124-3p for collagen synthesis inhibitions in atherosclerotic plaques

In an atherosclerotic model of high-fat-diet-fed ApoE^-/- mice, the level of miR-124-3p was observed to be inversely correlated with collagen expression in plaque areas. miR-124-3p modulated in vitro was found to be capable of down-regulating type I and type III collagen expression. And it may be accounted for the direct binding of miR-124-3p with P4HA1 mRNA, which is able to encode an enzyme regarded as collagen synthesis promoter. So, there is a hypothesis that plaques in advanced atherosclerosis could be wavered by P4HA1 targeting induced collagen inhibition of the miR-124-3p in VSMCs. miR-124-3p, a highly conserved miRNA detected in many tissues of the human body, is demonstrated to be downregulated in different cancers and might act as a tumor cell proliferation and migration inhibitors. 4-hydroxyproline plays an important role in the three-dimensional folding process of the newly synthesized procollagen, and among the hundreds of possible target genes of miR-124, p4HA1 acts as the catalyst for the formation of 4-hydroproline. Collagen chains cannot fold into triple helical molecules and are without stability at body temperature if P4H is absent. P4HA1 is a major alpha subunit of isoforms of P4H. Type I and type III synthesis in VSMCs can be enhanced by P4HA1 overexpression and it can be reduced by P4H inhibitor.

Figure 1. Molecular mechanism of cP4H1 in enhancing HIF-1 stability and cancer cell stemness in TNBC. (Ren Xu, et al. 2010)

References:

Xu R. P4HA1 is a new regulator of the HIF-1 pathway in breast cancer. Cell stress, 2019, 3(1): 27.
Chakravarthi B V S K, Pathi S S, Goswami M T, et al. The miR-124-prolyl hydroxylase P4HA1-MMP1 axis plays a critical role in prostate cancer progression. Oncotarget, 2014, 5(16): 6654.
Agarwal S, Behring M, Kim H G, et al. Targeting P4HA1 with a small molecule inhibitor in a colorectal cancer PDX model. Translational oncology, 2020, 13(4): 100754.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry