Last update 19 Sep 2024

WDR6

Last update 19 Sep 2024

Basic Info

Synonyms

WD repeat domain 6, WD repeat-containing protein 6, WDR6

Introduction

Enhances the STK11/LKB1-induced cell growth suppression activity. Negative regulator of amino acid starvation-induced autophagy.

Drugs associated with WDR6

XLIX

Target

WDR6

Mechanism

WDR6 inhibitors

Active Org.

Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital)

Originator Org.

Provincial Hospital Affiliated to Shandong First Medical University (Shandong Provincial Hospital)

Active Indication

Fatty Liver

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with WDR6

100 Translational Medicine associated with WDR6

0 Patents (Medical) associated with WDR6

Literatures (Medical) associated with WDR6

01 Dec 2024·Molecular Biology Reports

PABPN1 functions as a predictive biomarker in colorectal carcinoma

Article

Author: Yao, Li-Qian ; Gao, Xiao-Jiao ; Yan, Pei-Ci ; Shi, Li-Zhou ; Zhou, Ming-Hui ; Liang, Zhi-Wei ; Han, Wei ; Li, Rui ; Teng, Ya-Jie ; Wang, Qing-Hua

PURPOSEPABPN1 acts as a modulator of poly(A) tail length and alternative polyadenylation. This research was aimed to explore the role of PABPN1 in colorectal cancer (CRC).METHODSPublic databases were performed to analyze expression, location, roles of prognosis and tumor immunity and interaction with RNAs and proteins of PABPN1. To investigate PABPN1 expression in tissues, 78 CRC specimens were collected to conduct IHC, and 30 pairs of frozen CRC and corresponding adjacent normal tissues were used to conduct qRT-PCR and WB. In addition, in vitro experiments were then carried out to identify the role of PABPN1 in CRC.RESULTSCompared with normal tissues, PABPN1 expression was significant higher in CRC. Its high level predicted poor outcome of CRC. Th1 and Treg had significant negative relationships not only with PABPN1 expression, but also with six molecules interacting with PABPN1, including IFT172, KIAA0895L, RECQL4, WDR6, PABPC1 and NCBP1. In addition, PABPN1 had negative relationships with quite a few immune markers, such as CSF1R, IL-10, CCL2 and so on. In cellular experiments, silencing PABPN1 inhibited proliferation and promoted apoptosis in HCT-116 CRC cells.CONCLUSIONIn summary, PABPN1 might become a novel biomarker and correlate with tumor immunity in CRC.

01 Oct 2023·Psychological Medicine

Multiomic prioritisation of risk genes for anorexia nervosa

Article

Author: Cairns, Murray J ; Adams, Danielle M ; Reay, William R

AbstractBackgroundAnorexia nervosa (AN) is a psychiatric disorder associated with marked morbidity. Whilst AN genetic studies could identify novel treatment targets, integration of functional genomics data, including transcriptomics and proteomics, would assist to disentangle correlated signals and reveal causally associated genes.MethodsWe used models of genetically imputed expression and splicing from 14 tissues, leveraging mRNA, protein, and mRNA alternative splicing weights to identify genes, proteins, and transcripts, respectively, associated with AN risk. This was accomplished through transcriptome, proteome, and spliceosome-wide association studies, followed by conditional analysis and finemapping to prioritise candidate causal genes.ResultsWe uncovered 134 genes for which genetically predicted mRNA expression was associated with AN after multiple-testing correction, as well as four proteins and 16 alternatively spliced transcripts. Conditional analysis of these significantly associated genes on other proximal association signals resulted in 97 genes independently associated with AN. Moreover, probabilistic finemapping further refined these associations and prioritised putative causal genes. The gene WDR6, for which increased genetically predicted mRNA expression was correlated with AN, was strongly supported by both conditional analyses and finemapping. Pathway analysis of genes revealed by finemapping identified the pathway regulation of immune system process (overlapping genes = MST1, TREX1, PRKAR2A, PROS1) as statistically overrepresented.ConclusionsWe leveraged multiomic datasets to genetically prioritise novel risk genes for AN. Multiple-lines of evidence support that WDR6 is associated with AN, whilst other prioritised genes were enriched within immune related pathways, further supporting the role of the immune system in AN.

01 Oct 2023·Nature metabolism

Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice.

Article

Author: Song, Yongfeng ; Zhao, Jiajun ; Xu, Jiawen ; Yao, Zhenyu ; Wang, Dawei ; Yang, Rui ; Liu, Jun ; Wu, Yingjie ; Gao, Ling ; Gong, Ying ; Kong, Junjie ; Niu, Shaona ; Shao, Shanshan ; Fu, Lili ; Zhao, Xinya ; Wang, Xuemin ; Lin, Xiaoyan ; Xu, Yunyun ; Chen, Wenbin ; Zhang, Zhenhai ; Wan, Qiang ; Xuan, Qiuhui ; Proud, Christopher G ; Guo, Honglin ; Li, Qihang ; Liu, Sijin ; Bo, Tao ; Wang, Ximing ; Wang, Qian

Under normal conditions, insulin promotes hepatic de novo lipogenesis (DNL). However, during insulin resistance (IR), when insulin signalling is blunted and accompanied by hyperinsulinaemia, the promotion of hepatic DNL continues unabated and hepatic steatosis increases. Here, we show that WD40 repeat-containing protein 6 (WDR6) promotes hepatic DNL during IR. Mechanistically, WDR6 interacts with the beta-type catalytic subunit of serine/threonine-protein phosphatase 1 (PPP1CB) to facilitate PPP1CB dephosphorylation at Thr316, which subsequently enhances fatty acid synthases transcription through DNA-dependent protein kinase and upstream stimulatory factor 1. Using molecular dynamics simulation analysis, we find a small natural compound, XLIX, that inhibits the interaction of WDR6 with PPP1CB, thus reducing DNL in IR states. Together, these results reveal WDR6 as a promising target for the treatment of hepatic steatosis.

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WDR6

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