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Last update 23 Jan 2025

WLS

Last update 23 Jan 2025

Basic Info

Synonyms

C1orf139, EVI, FLJ23091

+ [9]

Introduction

Regulates Wnt proteins sorting and secretion in a feedback regulatory mechanism. This reciprocal interaction plays a key role in the regulation of expression, subcellular location, binding and organelle-specific association of Wnt proteins (PubMed:34587386). Plays also an important role in establishment of the anterior-posterior body axis formation during development (By similarity).

Drugs associated with WLS

YW-1128

Target

CTNNB1 x WLS

Mechanism

CTNNB1 inhibitors [+1]

Active Org.

Guangzhou Medical University [+1]

Originator Org.

University of Maryland

Active Indication

Carbohydrate Metabolism, Inborn Errors [+3]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NOV-1502

Target

CTNNB1 x RAS x WLS

Mechanism

CTNNB1 modulators [+2]

Active Org.

Yonsei University

Originator Org.

Yonsei University

Active Indication

Solid tumor

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

P-975

Target

WLS

Mechanism

WLS gene modulators

Active Org.

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Originator Org.

German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ)

Active Indication

Brain Cancer

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with WLS

100 Translational Medicine associated with WLS

0 Patents (Medical) associated with WLS

295

Literatures (Medical) associated with WLS

01 Jan 2025·Biomedicine & Pharmacotherapy

n-acetyl-l-cysteine stimulates bone healing by recovering the age-associated degenerative complications relative to osteoblastic Wntless ablation

Article

Author: Lee, Jeong-Chae ; Kim, Min-Hye ; Kook, Sung-Ho ; Poudel, Sher Bahadur ; So, Han-Sol ; Bhattarai, Govinda

Dysregulated Wnt signaling causes age-related characteristics such as oxidative stress, stem cell senescence, and abnormal bone homeostasis. Here we explored whether supplemental n-acetyl-l-cysteine (NAC) recovers the age-associated complications relative to osteoblastic Wntless (Wls) ablation and examined the possible mechanisms therein. For this work, we administered Col2.3-Cre;Wls^fl/fl mutant and littermate control (Wls^fl/fl) mice (14 weeks of age) with NAC (40 mM)-supplemented or NAC-free water for four weeks. A proportion of these mice received non-critical-sized femoral defects at 16 weeks of age. Blood, bone, and bone marrow (BM) samples were collected and adjusted for in vivo, ex vivo, and in vitro analyses. Osteoblastic Wls deletion delayed bone mass accrual and the healing of bone defects, stimulated osteoclastic activation and inflammatory factor expression, and decreased antioxidant enzyme activity in the BM. Osteoblastic Wls deletion also promoted oxidative stress, apoptosis, and senescence in BM stromal cells (BMSCs) and decreased BMSC' multipotencies. Supplementation of Wls^fl/fl mice with NAC enhanced bone mass accrual and regenerative bone healing via a Wnt signal-associated osteogenic activation. However, supplemental NAC induced new bone formation in the mutant mice by inhibiting the age-related complications of BM/BMSCs, as well as by restoring endogenous antioxidant system without any alterations in Wnt ligand secretion, hematopoiesis, and expression of osteogenic and growth factors. This study indicates that supplemental NAC protects mice against Wnt deficiency-mediated and age-associated degenerative complications. Overall, this study highlights the therapeutic potency of NAC for restoring the antioxidant system, stem cell function, and regenerative bone homeostasis in osteoblastic Wls-dispensable manner.

01 Oct 2024·PROTEOMICS

The temporal protein signature analyses of developing human deciduous molar tooth germ

Article

Author: Wu, Buling ; Xiong, Fu ; Hu, Liang ; Zhang, Jian ; Chen, Xiaohang ; Wei, Fengxiang ; Zhao, Guoqiang ; Li, Gaochi

AbstractThe tooth serves as an exemplary model for developmental studies, encompassing epithelial‐mesenchymal transition and cell differentiation. The essential factors and pathways identified in tooth development will help understand the natural development process and the malformations of mineralized tissues such as skeleton. The time‐dependent proteomic changes were investigated through the proteomics of healthy human molars during embryonic stages, ranging from the cap‐to‐early bell stage. A comprehensive analysis revealed 713 differentially expressed proteins (DEPs) exhibiting five distinct temporal expression patterns. Through the application of weighted gene co‐expression network analysis (WGCNA), 24 potential driver proteins of tooth development were screened, including CHID1, RAP1GDS1, HAPLN3, AKAP12, WLS, GSS, DDAH1, CLSTN1, AFM, RBP1, AGO1, SET, HMGB2, HMGB1, ANP32A, SPON1, FREM1, C8B, PRPS2, FCHO2, PPP1R12A, GPALPP1, U2AF2, and RCC2. Then, the proteomics and transcriptomics expression patterns of these proteins were further compared, complemented by single‐cell RNA‐sequencing (scRNA‐seq). In summary, this study not only offers a wealth of information regarding the molecular intricacies of human embryonic epithelial and mesenchymal cell differentiation but also serves as an invaluable resource for future mechanistic inquiries into tooth development.

01 Sep 2024·Autophagy

The Wolfram-like variant WFS1 ^E864K destabilizes MAM and compromises autophagy and mitophagy in human and mice

Article

Author: Bataillard, Méghane S. ; Tranebjærg, Lisbeth ; Delprat, Benjamin ; Richard, Elodie M. ; Patergnani, Simone ; Maurice, Tangui ; Cazevieille, Chantal ; Valéro, René ; Pinton, Paolo ; Alves, Stacy ; Danese, Alberto

Dominant variants in WFS1 (wolframin ER transmembrane glycoprotein), the gene coding for a mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) resident protein, have been associated with Wolfram-like syndrome (WLS). In vitro and in vivo, WFS1 loss results in reduced ER to mitochondria calcium (Ca²⁺) transfer, mitochondrial dysfunction, and enhanced macroautophagy/autophagy and mitophagy. However, in the WLS pathological context, whether the mutant protein triggers the same cellular processes is unknown. Here, we show that in human fibroblasts and murine neuronal cultures the WLS protein WFS1^E864K leads to decreases in mitochondria bioenergetics and Ca²⁺ uptake, deregulation of the mitochondrial quality system mechanisms, and alteration of the autophagic flux. Moreover, in the Wfs1^E864K mouse, these alterations are concomitant with a decrease of MAM number. These findings reveal pathophysiological similarities between WS and WLS, highlighting the importance of WFS1 for MAM's integrity and functionality. It may open new treatment perspectives for patients with WLS.Abbreviations: BafA1: bafilomycin A₁; ER: endoplasmic reticulum; HSPA9/GRP75: heat shock protein family A (Hsp70) member 9; ITPR/IP₃R: inositol 1,4,5-trisphosphate receptor; MAM: mitochondria-associated endoplasmic reticulum membrane; MCU: mitochondrial calcium uniporter; MFN2: mitofusin 2; OCR: oxygen consumption rate; ROS: reactive oxygen species; ROT/AA: rotenone+antimycin A; VDAC1: voltage dependent anion channel 1; WLS: Wolfram-like syndrome; WS: Wolfram syndrome; WT: wild-type.

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