MEN1 tumor-suppressor protein localizes to telomeres during meiosis

Kanya Suphapeetiporn, John M. Greally, Deepika Walpita, Terry Ashley, Allen E. Bale

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Multiple endocrine neoplasia type I is an autosomal dominant cancer predisposition syndrome caused by mutations in the tumor-suppressor gene MEN1. The gene encodes a nuclear protein, menin, with no recognized functional motifs. Menin has been shown negatively to regulate transcriptional activation mediated by JunD, although the significance of this interaction in normal cell physiology and how the absence of menin leads to tumorigenesis are unknown. Menin is highly expressed in testes. We used immunocytochemistry to explore its role in meiosis and found that it localizes exclusively at telomeres. JunD was not found at telomeres in meiotic cells. In view of elevated telomerase activity or abnormal telomere structure in virtually all malignancies, regulation of telomere function would be an appealing role for a tumor suppressor. However, menin does not specifically associate with telomeres in somatic cells, as indicated by lack of co-localization with the known telomeric protein TRF2. Cells overexpressing menin had normal telomerase activity, and tumors with homozygous MEN1 mutations showed no aberrations in telomere length, indicating that menin does not directly regulate telomerase activity. The role of menin at meiotic telomeres appears to be independent of JunD and may not have a counterpart in somatic cells. These results suggest that menin may play different roles in different tissues through interactions with different proteins.

Original languageEnglish (US)
Pages (from-to)81-85
Number of pages5
JournalGenes Chromosomes and Cancer
Volume35
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

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Multiple Endocrine Neoplasia Type 1
Tumor Suppressor Proteins
Telomere
Meiosis
Telomerase
Telomeric Repeat Binding Protein 2
Neoplasms
Cell Physiological Phenomena
Mutation
Nuclear Proteins
Tumor Suppressor Genes
Transcriptional Activation
Testis
Carcinogenesis
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

MEN1 tumor-suppressor protein localizes to telomeres during meiosis. / Suphapeetiporn, Kanya; Greally, John M.; Walpita, Deepika; Ashley, Terry; Bale, Allen E.

In: Genes Chromosomes and Cancer, Vol. 35, No. 1, 2002, p. 81-85.

Research output: Contribution to journalArticle

Suphapeetiporn, Kanya ; Greally, John M. ; Walpita, Deepika ; Ashley, Terry ; Bale, Allen E. / MEN1 tumor-suppressor protein localizes to telomeres during meiosis. In: Genes Chromosomes and Cancer. 2002 ; Vol. 35, No. 1. pp. 81-85.
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