WSB1: from homeostasis to hypoxia

Abstract

The wsb1 gene has been identified to be important in developmental biology and cancer. A complex transcriptional regulation of wsb1 yields at least three functional transcripts. The major expressed isoform, WSB1 protein, is a substrate recognition protein within an E3 ubiquitin ligase, with the capability to bind diverse targets and mediate ubiquitinylation and proteolytic degradation. Recent data suggests a new role for WSB1 as a component of a neuroprotective pathway which results in modification and aggregation of neurotoxic proteins such as LRRK2 in Parkinson’s Disease, via an unusual mode of protein ubiquitinylation.WSB1 is also involved in thyroid hormone homeostasis, immune regulation and cellular metabolism, particularly glucose metabolism and hypoxia. In hypoxia, wsb1 is a HIF-1 target, and is a regulator of the degradation of diverse proteins associated with the cellular response to hypoxia, including HIPK2, RhoGDI2 and VHL. Major roles are to both protect HIF-1 function through degradation of VHL, and decrease apoptosis through degradation of HIPK2. These activities suggest a role for wsb1 in cancer cell proliferation and metastasis. As well, recent work has identified a role for WSB1 in glucose metabolism, and perhaps in mediating the Warburg effect in cancer cells by maintaining the function of HIF1. Furthermore, studies of cancer specimens have identified dysregulation of wsb1 associated with several types of cancer, suggesting a biologically relevant role in cancer development and/or progression.Recent development of an inducible expression system for wsb1 could aid in the further understanding of the varied functions of this protein in the cell, and roles as a potential oncogene and neuroprotective protein.

Data-Mining Approach on Transcriptomics and Methylomics Placental Analysis Highlights Genes in Fetal Growth Restriction

“…It has been evidenced that protein ubiquitination is altered in IUGR and PE, particularly due to a modulation by oxidative stress, with an increased degradation of p53 and Mcl-1 proteins, contributing to the pathological mechanisms of the diseases (Rolfo et al, 2012). WSB1 (underexpressed here) mediates ubiquitination and proteolytic degradation, and is also involved in cell and glucose metabolism, playing a role in hypoxia-related mechanisms (Haque et al, 2016). USP5 (underexpressed here) codes for a deubiquitinating enzyme which has also been shown to play a role in cell cycle modulation.…”

WSB2 as a target of Hedgehog signaling promoted the malignant biological behavior of Xuanwei lung cancer through regulating Wnt/β-catenin signaling

“…To our current knowledge, numerous researches have found the frequently expression of WSB1 in various types of cancer ( 18 ). Such as, WSB1 knockdown significantly reduced the invasiveness of hormone receptor negative breast cancer cells ( 19 ). Furthermore, there was a research indicated that miR-592 could inhibit aerobic glycolysis and growth hepatocellular carcinoma through directly targeting WSB1 ( 20 ).…”

The Role of Immunogenetics in COVID-19

“…Another preprint leading with supervariants involved in COVID-19 mortality focuses on the possible role of rs60811869, an eQTL of gene of the E3 ubiquitin ligase WD Repeat And SOCS Box Containing 1 ( WSB1 ), in determining death rates among COVID-19 patients [ 170 , 171 ]. WSB1 is a particularly promising candidate, being involved in hormone homeostasis and hypoxia, as well as in the maturation of IL-21 receptor with IL-21 being a key player in humoral immunity and in the formation of the immune memory [ 172 , 173 , 174 , 175 , 176 ].…”