ArticleThe Journal of biological chemistry2018
The transmembrane protein TMEPAI induces myeloma cell apoptosis by promoting degradation of the c-Maf transcription factor.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- PMEPA1 Binds NEDD4L to Inhibit the Malignant Progression of Multiple Myeloma by Inactivating Wnt/β-Catenin Signaling.Cell biochemistry and biophysics · 2025Article
- BCL-2 dependence is a favorable predictive marker of response to therapy for chronic lymphocytic leukemia.Molecular cancer · 2025Article
- The role and regulation of Maf proteins in cancer.Biomarker research · 2023Review
- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
- Article
- The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology.Cancers · 2021Review
- Article
- TGF-β-Induced TMEPAI Promotes Epithelial-Mesenchymal Transition in Doxorubicin-Treated Triple-Negative Breast Cancer Cells via SMAD3 and PI3K/AKT Pathway Alteration.Breast cancer (Dove Medical Press) · 2021Article
- Anti-bacterial and anti-viral nanchangmycin displays anti-myeloma activity by targeting Otub1 and c-Maf.Cell death & disease · 2020Article
- The deubiquitinase USP7 stabilizes Maf proteins to promote myeloma cell survival.The Journal of biological chemistry · 2020Article
- PMEPA1 isoform a drives progression of glioblastoma by promoting protein degradation of the Hippo pathway kinase LATS1.Oncogene · 2020Article
- TMEPAI/PMEPA1 Is a Positive Regulator of Skeletal Muscle Mass.Frontiers in physiology · 2020Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TMEPAI (transmembrane prostate androgen-induced protein, also called prostate transmembrane protein, androgen-induced 1 (PMEPA1)) is a type I transmembrane (TM) protein, but its cellular function is largely unknown. Here, studying factors influencing the stability of c-Maf, a critical transcription factor in multiple myeloma (MM), we found that TMEPAI induced c-Maf degradation. We observed that TMEPAI recruited NEDD4 (neural precursor cell expressed, developmentally down-regulated 4), a WW domain-containing ubiquitin ligase, to c-Maf, leading to its degradation through the proteasomal pathway. Further investigation revealed that TMEPAI interacts with NEDD4 via its conserved PY motifs. Alanine substitution or deletion of these motifs abrogated the TMEPAI complex formation with NEDD4, resulting in failed c-Maf degradation. Functionally, TMEPAI suppressed the transcriptional activity of c-Maf. Of note, increased TMEPAI expression was positively associated with the overall survival of MM patients. Moreover, TMEPAI was down-regulated in MM cells, and re-expression of TMEPAI induced MM cell apoptosis. In conclusion, this study highlights that TMEPAI decreases c-Maf stability by recruiting the ubiquitin ligase NEDD4 to c-Maf for proteasomal degradation. Our findings suggest that the restoration of functional TMEPA1 expression may represent a promising complementary therapeutic strategy for treating patients with MM.
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