ArticleMolecular and cellular biology2004
Menin missense mutants associated with multiple endocrine neoplasia type 1 are rapidly degraded via the ubiquitin-proteasome pathway.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 116 citations in OpenAlex.
- Impaired transforming growth factor-β (TGF-β) transcriptional activity and cell proliferation control of a menin in-frame deletion mutant associated with multiple endocrine neoplasia type 1 (MEN1).The Journal of biological chemistry · 2012Trial
- Multiple endocrine neoplasia type 1 withJCEM case reports · 2026Article
- Familial MEN1 Syndrome with Atypical Renal Features and a Coexisting CLDN16 Variant: A Case Series.Journal of clinical medicine · 2025Article
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Molecular Pathophysiology of Parathyroid Tumorigenesis-The Lesson from a Rare Disease: The "MEN1 Model".International journal of molecular sciences · 2024Review
- Article
- Review
- Clinically Defined Mutations inCancer research communications · 2023Article
- Multi-omics analyses of MEN1 missense mutations identify disruption of menin-MLL and menin-JunD interactions as critical requirements for molecular pathogenicity.Epigenetics & chromatin · 2022Article
- Gastrin: From Physiology to Gastrointestinal Malignancies.Function (Oxford, England) · 2022Review
- A Novel Isogenic Human Cell-Based System for MEN1 Syndrome Generated by CRISPR/Cas9 Genome Editing.International journal of molecular sciences · 2021Article
- Review
- Understanding the Origins of Loss of Protein Function by Analyzing the Effects of Thousands of Variants on Activity and Abundance.Molecular biology and evolution · 2021Article
- Article
- Novel Germline c.105_107dupGCTGenes · 2020Article
- Disruption inScience advances · 2020Article
- Wild-type menin is rapidly degraded via the ubiquitin-proteasome pathway in a rat insulinoma cell line.Bioscience reports · 2019Article
- Disruption of the menin-MLL interaction triggers menin protein degradation via ubiquitin-proteasome pathway.American journal of cancer research · 2019Article
- Gastrin Induces Nuclear Export and Proteasome Degradation of Menin in Enteric Glial Cells.Gastroenterology · 2017Article
- Twenty years of menin: emerging opportunities for restoration of transcriptional regulation in MEN1.Endocrine-related cancer · 2017Review
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6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MEN1 is a tumor suppressor gene that is responsible for multiple endocrine neoplasia type 1 (MEN1) and that encodes a 610-amino-acid protein, called menin. While the majority of germ line mutations identified in MEN1 patients are frameshift and nonsense mutations resulting in truncation of the menin protein, various missense mutations have been identified whose effects on menin activity are unclear. For this study, we analyzed a series of menin proteins with single amino acid alterations and found that all of the MEN1-causing missense mutations tested led to greatly diminished levels of the affected proteins in comparison with wild-type and benign polymorphic menin protein levels. We demonstrate here that the reduced levels of the mutant proteins are due to rapid degradation via the ubiquitin-proteasome pathway. Furthermore, the mutants, but not wild-type menin, interact both with the molecular chaperone Hsp70 and with the Hsp70-associated ubiquitin ligase CHIP, and the overexpression of CHIP promotes the ubiquitination of the menin mutants in vivo. These findings reveal that MEN1-causing missense mutations lead to a loss of function of menin due to enhanced proteolytic degradation, which may be a common mechanism for inactivating tumor suppressor gene products in familial cancer.
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