TRIM32 triggers β-catenin signaling through ubiquitylation of AXIN1 to promote inflammatory factor-induced apoptosis of rat nucleus pulposus cells

Abstract

The dysregulation of ubiquitin ligase is the cause of many human diseases. Tripartite motif protein 32 (TRIM32) is an E3 ubiquitin ligase whose role in nucleus pulposus (NP) cell apoptosis is unclear. The expression of TRIM family protein and β-catenin in 40 NP tissue samples was detected by RT-PCR. Interleukin (IL)-1β or tumor necrosis factor (TNF)-α was used to treat rat NP cells. Knockdown and overexpression of Trim32 were achieved using specific siRNA and recombinant plasmids. Western blotting, RT-PCR, and flow cytometry were used to assess the expression of TRIM32/β-catenin and the apoptosis rate of NP cells. Coimmunoprecipitation was adopted to analyze the possible interactions between AXIN1 and TRIM32. In clinical samples, TRIM32 expression was of positive relevance with the expression of CTNNB1 (β-catenin). In vitro, apoptosis of IL-1β- or TNF-α-treated rat NP cells was induced through upregulated Trim32 expression and activated β-catenin signaling, whereas Trim32 siRNA and inhibition of β-catenin reversed the induction effect of cytokines. Further studies indicated that TRIM32 activated the β-catenin signaling pathway through ubiquitination of AXIN1, thereby regulating apoptosis. Collectively, this study reveals that TRIM32 promotes inflammatory factor-induced apoptosis of rat NP cells, in part by direct degradation of AXIN1 to trigger β-catenin signaling.

TRIM32 and Malin in Neurological and Neuromuscular Rare Diseases

“…Likewise, TRIM32 may also regulate satellite-cell differentiation by activating the Wnt/β-catenin pathway or by potentially affecting Wnt/β-catenin downstream miRNAs, such as miR-133b and miR-206, which promote Pax7 downregulation and, hence, adult muscle progenitor cell differentiation during muscle regeneration [95][96][97]. However, how and whether this is related to the occurrence of LGMDR8 is presently unknown.…”

TRIM37 promotes gallbladder cancer proliferation by activating the Wnt/β-catenin pathway via ubiquitination of Axin1

“…In GBC cells, TRIM37 has been found to interact with Wnt/β‑catenin signaling pathway, although the mechanisms behind this remain unknown [ 11 , 12 , [18] , [19] , [20] , [21] ]. It has been shown in previous studies that the E3 ubiquitin ligases, such as RNF146, TRIM11, TRIM32, TRIM54, TRIM65 and UBE3C promote various cancers by triggering Wnt/β-catenin signaling via degradation of Axin1 [22] , [23] , [24] , [25] , [26] , [27] . Axin1 and GSK-3β are two key regulators of the Wnt/β-Catenin pathway.…”

Inhibition of TRIM32 Attenuates the Apoptosis, Oxidative Stress and Inflammatory Injury of Podocytes Induced by High Glucose by Affecting the Akt/GSK-3β/Nrf2 Pathway

“…Moreover, the knockdown of TRIM32 alleviates oxygen-glucose deprivation-induced apoptosis of hippocampal neurons [42]. The silencing of TRIM32 decreases the apoptosis of nucleus pulposus cells induced by IL-1β or TNF-α [43]. Notably, TRIM32 expression is induced by hydrogen peroxide or rotenone in human embryonic kidney cells, and TRIM32 up-regulation enhances human embryonic kidney cells to hydrogen peroxide-or rotenone-induced cell death [23].…”