P4HB

Official Full Name

prolyl 4-hydroxylase subunit beta

Organism

Homo sapiens

GeneID

5034

Background

This gene encodes the beta subunit of prolyl 4-hydroxylase, a highly abundant multifunctional enzyme that belongs to the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, this enzyme is involved in hydroxylation of prolyl residues in preprocollagen. This enzyme is also a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds. Other known functions include its ability to act as a chaperone that inhibits aggregation of misfolded proteins in a concentration-dependent manner, its ability to bind thyroid hormone, its role in both the influx and efflux of S-nitrosothiol-bound nitric oxide, and its function as a subunit of the microsomal triglyceride transfer protein complex. [provided by RefSeq, Jul 2008]

Synonyms

DSI; GIT; PDI; PHDB; PDIA1; PO4DB; PO4HB; PROHB; CLCRP1; ERBA2L; P4Hbeta;

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Detailed Information

P4HB functions as a hypoxia targeted gene in Gastric cancer invasion and metastasis

There are many reports about the progress of the treatment for gastric cancer (GC), which is the most common malignant tumor of the digestive system and the second leading cause of cancer-related death. The research of founding the early diagnosis and control of invasion and metastasis of this disease is important, and it can be resorted to biomarker identification and the underlying molecular mechanisms revelation in GC. Hypoxic microenvironment in the tumor is evidenced to be associated with its progression and metastasis. Several hypoxia inductions factors (HIFs) are synergistic in the regulation of the response of cells to hypoxia, and responsible for accelerating cell dissemination and angiogenesis promotion. Differently expressed genes have relatedness with signaling pathways were revealed by biochips and next-generation sequencing (NGS) in medical oncology. Subsequent to those findings, some molecular targeted drugs have been approved and used in clinical practice, while their efficacy has not met the expectations, where we can see the anticipated huge breakthrough resulting from their use. As a highly abundant multifunctional enzyme, prolyl 4-hydroxylase beta polypeptide (P4HB) functions as an endoplasmic reticulum (ER) chaperone for the prevention of the misfolded proteins aggregation. Besides the over-expression of P4HB was confirmed in GC tissue and hepatocellular carcinoma, it is also closely linked with drug resistance in malignant glioma and lymphatic metastases of cancers, which is further confirmed by proteomic and protein functional studies. In GC cells and gastric tissue samples, examination of the P4HB and HIF-1α evaluated the association between them and GC invasion and metastasis phenotype, where HIF-1α can suppress the expression of P4HB and promote GC invasion and metastasis.

P4HB influences chemoresistance in liver cancer cells via regulating EMS and β-catenin/Snail pathway

As the sixth most common cancer and the second leading cause of cancer-associated mortality worldwide, liver cancer has drawn much attention. While the most commonly used treatment method for liver cancer, chemotherapy has not got efficacious results in certain patients. And the prognosis of patients with HCC cannot fulfill the anticipations. So fully understanding the molecular mechanisms of ADR resistance in liver cancer may help to improve liver cancer prognosis and avoid chemoresistance. In addition to the important role of EMT played in the physiological process, it is also closely associated with drug -resistance and tumor metastasis, in which Snail and β-catenin severed as two significant regulators. Knockdown of P4HB can significantly decrease snail expression in HepG2/ADR cells in comparison with the parental HepG2 cell lines.

Figure 1. Involvement of P4HB in signaling pathway in charge of chemosensitivity. (Jun zhang, et al. 2019)

References:

Zhang J, Guo S, Wu Y, et al. P4HB, a novel hypoxia target gene related to gastric cancer invasion and metastasis. BioMed research international, 2019.
Ma X, Wang J, Zhuang J, et al. P4HB modulates epithelial‑mesenchymal transition and the β‑catenin/Snail pathway influencing chemoresistance in liver cancer cells. Oncology letters, 2020, 20(1): 257-265.

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