Menin molecular interactions: insights into normal functions and tumorigenesis
S K Agarwal1, P A Kennedy, P C Scacheri
1National Institute of Diabetes and Digestive and Kidney Diseases/NIH, 9000 Rockville Pike, Bethesda, MD 20892-1802, USA. SunitaA@intra.niddk.nih.gov
Abstract:
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease predisposed by heterozygous germline mutations in the MEN1 tumor suppressor gene. Biallelic loss of MEN1 resulting from small mutation and/or loss of heterozygosity occurs in a large tissue spectrum of MEN1 tumors or non-hereditary tumors. Mouse models of MEN1 underexpression or overexpression have also supported the tumor-suppressor effect of the MEN1 gene. Menin, the 610-amino-acid protein encoded by MEN1, is expressed ubiquitously and found predominantly in the nucleus. Sequence analyses do not reveal motifs of known function other than two nuclear localization sequences. Menin has been found to partner in vitro with a variety of proteins that comprise transcription factors, DNA processing factors, DNA repair proteins, and cytoskeletal proteins. The diverse functions of menin interactors suggest roles for menin in multiple biological pathways. Inactivation of menin switches its JunD partner from a downstream action of growth suppression to growth promotion. This is a plausible mechanism for menin tumorigenesis.
Insights
Multiple endocrine neoplasia type 1 (MEN1) arises from mutations in the MEN1 gene. Loss of the menin protein disrupts its interaction with JunD, promoting tumor growth.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by germline mutations in the MEN1 tumor suppressor gene.
- Biallelic inactivation of the MEN1 gene, through mutation or loss of heterozygosity, is implicated in both hereditary and sporadic tumors.
- The MEN1 gene encodes the menin protein, a nuclear factor involved in various cellular processes.
Purpose of the Study:
- To investigate the role of the menin protein in tumor suppression.
- To elucidate the molecular mechanisms underlying menin's function in tumorigenesis.
Main Methods:
- Analysis of MEN1 gene mutations and protein expression in tumors.
- In vitro studies to identify menin-interacting proteins.
- Examination of menin's interaction with JunD and its effect on cell growth.
Main Results:
- Menin protein interacts with diverse cellular proteins, including transcription factors like JunD.
- Inactivation of menin alters its interaction with JunD, shifting its function from growth suppression to growth promotion.
- This switch in menin-JunD interaction provides a potential mechanism for MEN1-associated tumorigenesis.
Conclusions:
- The menin protein plays a critical role in tumor suppression through its interactions with other proteins.
- Dysregulation of the menin-JunD pathway is a key factor in the development of MEN1-related tumors.
More Related Videos
06:54Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
09:37Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Related Concept Videos
02:23Abnormal Proliferation
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...