PAQR4

Official Full Name

progestin and adipoQ receptor family member 4

Organism

Homo sapiens

Gene ID

124222

Background

Enables molecular adaptor activity. Involved in protein stabilization and regulation of ceramide biosynthetic process. Located in Golgi membrane. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

ARTS; DFN2; PRSI; CMTX5; DFNX1; PRS-I; PPRibP

Cat.No.	Product Name	Price
CSC-DC011295	Panoply™ Human PAQR4 Knockdown Stable Cell Line	Inquiry
CSC-SC011295	Panoply™ Human PAQR4 Over-expressing Stable Cell Line	Inquiry
CSC-RT1275	Human PAQR4 Knockout Cell Line-HeLa	Inquiry
CLKO-1128	PAQR4 KO Cell Lysate-HeLa	Inquiry

Cat.No.	Product Name	Price
AD11803Z	Human PAQR4 adenoviral particles	Inquiry
LV20965L	human PAQR4 (NM_152341) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHG042671	shRNA set against Rat Paqr4(NM_001017377.1)	Inquiry
SHG042739	shRNA set against Mouse Paqr4(NM_023824.3)	Inquiry
SHG042805	shRNA set against Human PAQR4(NM_152341.3)	Inquiry
SHH370584	shRNA set against Human PAQR4 (NM_152341.3)	Inquiry
SHH370588	shRNA set against Mouse PAQR4 (NM_023824.3)	Inquiry
SHH370592	shRNA set against Rat PAQR4 (NM_001017377.1)	Inquiry

Cat.No.	Product Name	Price
CDFR003438	Rat Paqr4 cDNA Clone(NM_001017377.1)	Inquiry
MiUTR1H-07504	PAQR4 miRNA 3'UTR clone	Inquiry
MiUTR1M-08893	PAQR4 miRNA 3'UTR clone	Inquiry
MiUTR1R-05619	PAQR4 miRNA 3'UTR clone	Inquiry
CDCB182274	Rabbit PAQR4 ORF clone (XM_008250626.1)	Inquiry
CDCR025048	Mouse Paqr4 ORF clone (NM_023824.3)	Inquiry
CDCR370428	Rat Paqr4 ORF Clone(NM_001017377.1)	Inquiry
CDCS410209	Human PAQR4 ORF Clone (BC033703)	Inquiry

Detailed Information

PAQR4 promotes chemoresistance in non-small cell lung cancer through Nrf2 protein degradation inhibition

As the predominant cause of cancer-related deaths among the main types of lung cancers, non-small cell lung cancer (NSCLC), which includes lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC) and large-cell lung carcinoma, occupies approximately 85% of all lung cancer, with a poor 5-year survival of only 15%. The prognosis of this disease is still poor due to the presence of locally advanced metastatic tumors in most patients at the time of diagnosis even though there is a big advance in treatment options including surgery, chemotherapy, radiation and targeted therapies. Tyrosine kinase inhibitors (TKIs) targeting EGFR or ALK-fusion proteins used in clinical trials have a significant increase in the 5-year survival rate of NSCLC. Sensitivity to chemotherapy at the early stage and drug resistance in the late stage of most patients with NSCLC put forward the need for the identification of novel targets and the development of personalized medicine in the future.

As one member of the 11 members (PAQR1 to PAQR11) consisted PAQR family, PAQR4 (Progestin and AdipoQ receptor 4) was predicted to be with 7 transmembrane domains, thus being distinctive from the traditional GPCR (G-protein coupled receptor) proteins in topology. There has already existed extensive investigation of PAQR3, which is a close homologue of PAQR4, and downregulation of PAQR3 can be found in different types of human cancers like colon cancer, gastric cancer, bladder cancer, breast cancer and so on. However, analysis of PAQR4 in the ONCOMINE database revealed that high expression of PAQR44 can be found in human breast cancers. A collective data of cellular, animal and human levels demonstrated the tumorigenic effect of PAQR4 on human breast cancers has relatedness with its modulatory activity on protein degradation of CDK4.

As one member of the Progestin and AdipoQ receptor family (PAQR) family, PAQR4 was identified to be a new differentially expressed gene by the cross-value association analysis (CVAA) method in the pan-cancer dataset. PAQR proteins of human share high conservation with the mouse orthologues. In this family, prototypes including PAQR5-8 function as membrane receptors for progesterone, and PAQR1 and PAQR2 work as surface receptors for adiponectin to play roles in metabolic regulation. The closest homologue of PAQR4, PAQR3 has been recently discovered as a deregulated tumor suppressor in various types of human cancers for its negative regulation of the Ras/Raf/MEK/ERK signaling cascade. Antagonistic actions between PAQR4 and SKP2 can give contributions to the regulation of cell proliferation and manipulations upon the CDK4 protein level. PAQR4 was found to be increased in NSCLC cancer cell lines, which is also accompanied by many mutations. High expression of PAQR4 has been demonstrated to be correlated with a worse clinical outcome, and knockdown of it can suppress cell proliferation via inducing apoptosis. Interaction between Nrf2 and Keap1 can be blocked by overexpressing PAQR4.

Figure 1. PAQR4 promotes chemoresistance in non-small cell lung cancer by inhibiting Nrf2 protein degradation. (Peifang Xu, et al. 2020)

References:

Xu P, Jiang L, Yang Y, et al. PAQR4 promotes chemoresistance in non-small cell lung cancer through inhibiting Nrf2 protein degradation[J]. Theranostics, 2020, 10(8): 3767.
Altorki N K, Markowitz G J, Gao D, et al. The lung microenvironment: an important regulator of tumour growth and metastasis[J]. Nature Reviews Cancer, 2019, 19(1): 9-31.

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