Tags

Type your tag names separated by a space and hit enter

Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin modifications and transcription regulation.
Nat Clin Pract Endocrinol Metab. 2006 Oct; 2(10):562-70.NC

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by tumors of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands, as well as by neuroendocrine carcinoid tumors, often at a young age. Causal to the syndrome are germline mutations of the MEN1 tumor-suppressor gene. Identification of gene-mutation carriers has enabled presymptomatic diagnosis and treatment of MEN1-related lesions. The product of the MEN1 gene is the nuclear protein menin. Recent observations indicate several functions for menin in the regulation of transcription, serving either as a repressor or as an activator: menin interacts with the activator-protein-1-family transcription factor JunD, changing it from an oncoprotein into a tumor-suppressor protein, putatively by recruitment of histone deacetylase complexes; menin maintains transforming growth factor beta mediated signal transduction involved in parathyroid hormone and prolactin gene expression; and menin is an integral component of histone methyltransferase complexes. In this capacity menin is a regulator of expression of the cyclin-dependent-kinase inhibitors p18INK4C and p27Kip1; furthermore, menin serves as a co-activator of estrogen receptor mediated transcription, by recruiting methyltransferase activity to lysine 4 of histone 3 at the estrogen responsive TFF1(pS2) gene promoter. We propose that menin links transcription-factor function to histone-modification pathways and that this is crucial for MEN1 tumorigenesis. Understanding the molecular pathology of MEN1 tumorigenesis will lead to new therapeutic strategies.

Authors+Show Affiliations

Department of Internal Medicine and Endocrinology, University Medical Center Utrecht, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17024155

Citation

Dreijerink, Koen Ma, et al. "Mechanisms of Disease: Multiple Endocrine Neoplasia Type 1-relation to Chromatin Modifications and Transcription Regulation." Nature Clinical Practice. Endocrinology & Metabolism, vol. 2, no. 10, 2006, pp. 562-70.
Dreijerink KM, Höppener JW, Timmers HM, et al. Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin modifications and transcription regulation. Nat Clin Pract Endocrinol Metab. 2006;2(10):562-70.
Dreijerink, K. M., Höppener, J. W., Timmers, H. M., & Lips, C. J. (2006). Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin modifications and transcription regulation. Nature Clinical Practice. Endocrinology & Metabolism, 2(10), 562-70.
Dreijerink KM, et al. Mechanisms of Disease: Multiple Endocrine Neoplasia Type 1-relation to Chromatin Modifications and Transcription Regulation. Nat Clin Pract Endocrinol Metab. 2006;2(10):562-70. PubMed PMID: 17024155.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of disease: multiple endocrine neoplasia type 1-relation to chromatin modifications and transcription regulation. AU - Dreijerink,Koen Ma, AU - Höppener,Jo Wm, AU - Timmers,Ht Marc, AU - Lips,Cornelis Jm, PY - 2005/12/16/received PY - 2006/04/27/accepted PY - 2006/10/7/pubmed PY - 2006/11/15/medline PY - 2006/10/7/entrez SP - 562 EP - 70 JF - Nature clinical practice. Endocrinology & metabolism JO - Nat Clin Pract Endocrinol Metab VL - 2 IS - 10 N2 - Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by tumors of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands, as well as by neuroendocrine carcinoid tumors, often at a young age. Causal to the syndrome are germline mutations of the MEN1 tumor-suppressor gene. Identification of gene-mutation carriers has enabled presymptomatic diagnosis and treatment of MEN1-related lesions. The product of the MEN1 gene is the nuclear protein menin. Recent observations indicate several functions for menin in the regulation of transcription, serving either as a repressor or as an activator: menin interacts with the activator-protein-1-family transcription factor JunD, changing it from an oncoprotein into a tumor-suppressor protein, putatively by recruitment of histone deacetylase complexes; menin maintains transforming growth factor beta mediated signal transduction involved in parathyroid hormone and prolactin gene expression; and menin is an integral component of histone methyltransferase complexes. In this capacity menin is a regulator of expression of the cyclin-dependent-kinase inhibitors p18INK4C and p27Kip1; furthermore, menin serves as a co-activator of estrogen receptor mediated transcription, by recruiting methyltransferase activity to lysine 4 of histone 3 at the estrogen responsive TFF1(pS2) gene promoter. We propose that menin links transcription-factor function to histone-modification pathways and that this is crucial for MEN1 tumorigenesis. Understanding the molecular pathology of MEN1 tumorigenesis will lead to new therapeutic strategies. SN - 1745-8366 UR - https://www.unboundmedicine.com/medline/citation/17024155/Mechanisms_of_disease:_multiple_endocrine_neoplasia_type_1_relation_to_chromatin_modifications_and_transcription_regulation_ L2 - http://www.diseaseinfosearch.org/result/4954 DB - PRIME DP - Unbound Medicine ER -