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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors

Thomas A Milne1, Christina M Hughes, Ricardo Lloyd

  • 1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 11, 2005
PubMed

Insights

Multiple Endocrine Neoplasia type 1 (MEN1) tumor suppressor menin regulates cell growth by controlling cyclin-dependent kinase inhibitors. Menin and MLL proteins cooperate to activate gene expression, preventing tumor development.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Mutations in the MEN1 gene cause Multiple Endocrine Neoplasia type 1 (MEN1) syndrome.
  • MEN1 syndrome involves parathyroid hyperplasia and tumors of the pituitary and pancreatic islets.
  • The tumor suppressor mechanism of MEN1 is not fully understood.

Purpose of the Study:

  • To elucidate the tumor suppressor mechanism of the MEN1 gene.
  • To investigate the interaction of menin with other proteins in gene regulation.
  • To determine the role of menin in regulating cell growth.

Main Methods:

  • Investigated the interaction of menin with Mixed Lineage Leukemia (MLL) proteins.
  • Analyzed the effect of menin and MLL on the expression of cyclin-dependent kinase inhibitors p27Kip1 and p18Ink4c.
  • Assessed the impact of menin and MLL loss of function on cell growth.

Main Results:

  • Menin directly regulates the expression of p27Kip1 and p18Ink4c.
  • Menin recruits MLL to the promoters and coding regions of p27Kip1 and p18Ink4c, activating transcription.
  • Loss of menin or MLL function leads to decreased p27Kip1 and p18Ink4c expression and deregulated cell growth.

Conclusions:

  • Cooperative interaction between menin and MLL in regulating cyclin-dependent kinase inhibitor transcription is crucial for menin's tumor suppressor activity.
  • This mechanism highlights a key pathway involved in MEN1 pathogenesis.
  • Targeting this pathway may offer therapeutic strategies for MEN1-associated tumors.

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