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MLL 5 protein forms intranuclear foci, and overexpression inhibits cell cycle progression

Lih-Wen Deng1, Isaac Chiu, Jack L Strominger

  • 1Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.

Proceedings of the National Academy of Sciences of the United States of America
|January 14, 2004
PubMed

Insights

The mammalian MLL5 gene, a component of the trithorax group, plays a role in cell growth. MLL5 protein localizes to the nucleus and its overexpression causes cell cycle arrest, suggesting involvement in chromatin remodeling.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • The MLL5 gene, part of the mammalian trithorax group, is located on chromosome band 7q22.
  • This region is frequently deleted in acute myeloid malignancies, indicating MLL5's potential role in these cancers.

Purpose of the Study:

  • To investigate the cellular localization and function of the MLL5 protein.
  • To identify domains within MLL5 responsible for its nuclear localization and foci accumulation.
  • To determine the effect of MLL5 overexpression on cell cycle progression.

Main Methods:

  • Constructing and transfecting tagged MLL5 cDNA (FLAG-V5) into 293T cells.
  • Utilizing immunofluorescence staining to determine protein localization.
  • Employing MLL5-truncated mutants fused with GFP to map functional domains.
  • Assessing cell cycle progression via BrdUrd incorporation and response to nocodazole.

Main Results:

  • MLL5 protein localizes to the nucleus, excluding nucleoli, with a speckled distribution.
  • A specific domain (residues 945-1,156) was identified as crucial for foci accumulation.
  • Overexpression of MLL5 led to G1 phase cell cycle arrest, evidenced by delayed mitotic entry and reduced BrdUrd incorporation.

Conclusions:

  • MLL5 forms intranuclear protein complexes.
  • These complexes are implicated in chromatin remodeling processes.
  • MLL5 may function as a cellular growth suppressor.

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