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TRIM32 triggers β-catenin signaling through ubiquitylation of AXIN1 to promote inflammatory factor-induced apoptosis of rat nucleus pulposus cells
- Source :
- American journal of physiology. Cell physiology. 318(3)
- Publication Year :
- 2020
-
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.
- Subjects :
- 0301 basic medicine
Adult
Male
Nucleus Pulposus
Physiology
Ubiquitin-Protein Ligases
Apoptosis
Rats, Sprague-Dawley
Tripartite Motif Proteins
03 medical and health sciences
0302 clinical medicine
Tripartite Motif
Ubiquitin
Axin Protein
AXIN1
medicine
Animals
Humans
Cells, Cultured
beta Catenin
biology
Chemistry
Ubiquitination
Cell Biology
Middle Aged
Ubiquitin ligase
Cell biology
Rats
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
biology.protein
β catenin signaling
Female
Nucleus
Transcription Factors
Subjects
Details
- ISSN :
- 15221563
- Volume :
- 318
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Cell physiology
- Accession number :
- edsair.doi.dedup.....47d430d62df523612ff635978bcb9c5e