Asymmetric proteasome segregation as a mechanism for unequal partitioning of the transcription factor T-bet during T lymphocyte division

Immunity. 2011 Apr 22;34(4):492-504. doi: 10.1016/j.immuni.2011.03.017. Epub 2011 Apr 14.

Abstract

Polarized segregation of proteins in T cells is thought to play a role in diverse cellular functions including signal transduction, migration, and directed secretion of cytokines. Persistence of this polarization can result in asymmetric segregation of fate-determining proteins during cell division, which may enable a T cell to generate diverse progeny. Here, we provide evidence that a lineage-determining transcription factor, T-bet, underwent asymmetric organization in activated T cells preparing to divide and that it was unequally partitioned into the two daughter cells. This unequal acquisition of T-bet appeared to result from its asymmetric destruction during mitosis by virtue of concomitant asymmetric segregation of the proteasome. These results suggest a mechanism by which a cell may unequally localize cellular activities during division, thereby imparting disparity in the abundance of cell fate regulators in the daughter cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Polarity
  • Cells, Cultured
  • Mice
  • Mice, Inbred C57BL
  • Mitosis*
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism*
  • T-Box Domain Proteins / immunology*
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*

Substances

  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Proteasome Endopeptidase Complex

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