P3H4

Last update 08 May 2025

Basic Info

Synonyms

Endoplasmic reticulum protein SC65, Leprecan-like protein 4, LEPREL4

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Introduction

Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linking of collagen fibrils. Required for normal bone density and normal skin stability via its role in hydroxylation of lysine residues in collagen alpha chains and in collagen fibril assembly.

100 Clinical Results associated with P3H4

100 Translational Medicine associated with P3H4

0 Patents (Medical) associated with P3H4

Literatures (Medical) associated with P3H4

18 Dec 2024·Science Translational Medicine

Dextromethorphan inhibits collagen and collagen-like cargo secretion to ameliorate lung fibrosis

Article

Author: Lauer, David ; Jung, Juan ; Oorschot, Viola ; Duerr, Julia ; Haberkant, Per ; Mall, Marcus A ; Halavatyi, Aliaksandr ; Stein, Frank ; Gote-Schniering, Janine ; Khan, Muzamil M. ; Tischer, Christian ; Becher, Isabelle ; Muley, Thomas ; Neumann, Beate ; Khan, Arif M. ; Zukowska, Joanna ; Benes, Vladimir ; Galea, George ; Savitski, Mikhail ; Grassi, Alessandro ; Winter, Hauke ; Tuechler, Nadine ; de la Cueva, Ernesto ; Landry, Jonathan J. M. ; Jung, Ferris ; Pepperkok, Rainer

Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, no cure for pulmonary fibrosis has yet been found. We screened a drug library and found that dextromethorphan (DXM), a cough expectorant, reduced the amount of excess fibrillar collagen deposited in the ECM in cultured primary human lung fibroblasts, a bleomycin mouse model, and a cultured human precision-cut lung slice model of lung fibrosis. The reduced extracellular fibrillar collagen upon DXM treatment was due to reversible trafficking inhibition of collagen type I (COL1) in the endoplasmic reticulum (ER) in TANGO1- and HSP47-positive structures. Mass spectrometric analysis showed that DXM promoted hyperhydroxylation of proline and lysine residues on various collagens (COL1, COL3, COL4, COL5, COL7, and COL12) and latent transforming growth factor–β–binding protein (LTBP1 and LTBP2) peptides, coinciding with their secretion block. Additionally, proteome profiling of DXM-treated cells showed increased thermal stability of prolyl-hydroxylases P3H2, P3H3, P3H4, P4HA1, and P4HA2, suggesting a change in their activity. Transcriptome analysis of profibrotic stimulated primary human lung fibroblasts and human ex vivo lung slices after DXM treatment showed activation of an antifibrotic program through regulation of multiple pathways, including the MMP-ADAMTS axis, WNT signaling, and fibroblast-to-myofibroblast differentiation. Together, these data obtained from in vitro, in vivo, and ex vivo models of lung fibrogenesis show that DXM has the potential to limit fibrosis through inhibition of COL1 membrane trafficking in the ER.

01 Jan 2024·Cellular Signalling

METTL3 regulates the proliferation, metastasis and EMT progression of bladder cancer through P3H4

Article

Author: Han, Cong-Hui ; Zhang, Qian-Jin ; Dong, Yang ; Wu, Wei ; Hao, Lin ; Shi, Zhen-Duo ; He, Hou-Guang ; Hong, Si-Hao ; Zhang, Jun-Jie ; Liu, Chun-Hui

Bladder cancer, the most common malignant tumor in the urinary system, exhibits significantly up-regulated expression of P3H4, which is associated with pathological factors. The objective of this study was to elucidate the underlying mechanism of P3H4 in bladder cancer. Initially, we analyzed P3H4 gene expression using the TCGA database and evaluated P3H4 levels in clinical samples and various bladder cell lines. P3H4 was found to be markedly overexpressed in bladder cancer samples. Subsequently, bladder cancer cells were transfected with shRNA targeting P3H4 (sh-P3H4), sh-METTL3, and P3H4 overexpression vectors (P3H4 OE). Viability, migration, and invasion of bladder cancer cells were assessed using CCK-8, wound healing, and transwell assays. Western blot analysis was performed to determine the levels of EMT-associated proteins, while RNA stability assays determined the half-life of P3H4. Knockdown of P3H4 resulted in inhibition of bladder cancer cell proliferation, migration, invasion, and EMT progression. Mechanistically, METTL3 was found to regulate the mRNA stability of P3H4 in bladder cancer. Moreover, overexpression of P3H4 reversed the inhibitory effects of METTL3 knockdown on bladder cancer cell behaviors. Stable cell lines were established by infecting EJ cells with lentiviral vectors containing sh-METTL3 or P3H4 OE. These cells were then implanted into the skin of BALB/c nude mice, and IHC analysis was used to analyze the expression levels of EMT-associated proteins. In vivo studies demonstrated that inhibition of METTL3 suppressed bladder cancer growth and EMT through P3H4. In conclusion, our findings suggest that METTL3 regulates the proliferation, metastasis, and EMT progression of bladder cancer through P3H4, highlighting its potential as a therapeutic target.

01 Aug 2023·Veterinary microbiology

The orf virus 129 protein can inhibit immune responses by interacting with host complement C1q binding protein in goat turbinate bone cells.

Article

Author: Zhu, Jiangjiang ; Ren, Yupeng ; Xiang, Hua ; Dan, Yixin ; Yang, Lu ; Yang, Falong ; Zhang, Huanrong ; He, Honghong

OBJECTIVEContagious ecthyma is a severe and highly contagious disease caused by an orf virus (ORFV). The virus is responsible for substantial economic losses in the goat industry and threatens humans. We previously determined the role of ORFV129 protein, one of the five ankyrin-repeat proteins coded by the orf genome, in suppressing the transcription of pro-inflammatory cytokines IL-6, IL-1β and IFN-γ. In the present study, we identified 14 cellular proteins (complement C1q binding protein [C1QBP], MCM7, EIF5A, PKM, SLC6A, TSPAN6, ATP6AP2, GPS1, MMADHC, HSPB6, SLC35B1, MTF1, P3H4, and IL15RA) that interact with ORFV129 using a yeast two-hybrid system in goat turbinate bone cells (GFTCs). The interaction between ORFV129 and (C1QBP), an immune-related protein, was confirmed using immunofluorescence co-localization and co-immunoprecipitation assays. C1QBP overexpression inhibited ORFV replication, whereas the knockdown of C1QBP promoted ORFV replication in GFTCs. Furthermore, ORFV or ORFV129 increased C1QBP expression in GFTCs, indicated that ORFV129-C1QBP interaction might contribute to the ORFV-induced host immune process. In addition, our research showed that ORFV increased the expression of ORFV129, cytokine IL-6, IL-1β and IFN-γ. C1QBP overexpression induced IFN-γ production and reduced IL-6 and IL-1β production. Conversely, C1QBP knockdown induced IL-1β production and reduced IFN-γ and IL-1β production. Moreover, augmentation of ORFV129 expression enhanced the inhibition of the secretion of cytokines IL-6, IL-1β, and IFN-γ induced by the altered expression of C1QBP. These findings suggest different downstream pathways might be involved in regulating different cytokines induced by ORFV129 expression in GFTCs.

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P3H4

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