Asymmetric Proteasome Segregation as a Mechanism for Unequal Partitioning of the Transcription Factor T-bet during T Lymphocyte Division

被引:141
作者
Chang, John T. [1 ,2 ]
Ciocca, Maria L. [1 ,2 ]
Kinjyo, Ichiko [1 ,2 ]
Palanivel, Vikram R. [1 ,2 ]
McClurkin, Courtney E. [1 ,2 ]
De Jong, Caitlin S. [1 ,2 ]
Mooney, Erin C. [1 ,2 ]
Kim, Jiyeon S. [1 ,2 ]
Steinel, Natalie C. [1 ,2 ]
Oliaro, Jane [3 ]
Yin, Catherine C. [4 ]
Florea, Bogdan I. [5 ]
Overkleeft, Herman S. [5 ]
Berg, Leslie J. [4 ]
Russell, Sarah M. [3 ,6 ]
Koretzky, Gary A. [1 ,2 ,7 ]
Jordan, Martha S. [7 ]
Reiner, Steven L. [1 ,2 ]
机构
[1] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Med, Philadelphia, PA 19104 USA
[3] Peter MacCallum Canc Ctr, Immune Signalling Lab, Melbourne, Vic 2002, Australia
[4] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA
[5] Leiden Univ, NL-2333 CC Leiden, Netherlands
[6] Swinburne Univ Technol, Fac Engn & Ind Sci, Ctr MicroPhoton, Hawthorn, Vic 3122, Australia
[7] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
基金
澳大利亚国家健康与医学研究理事会;
关键词
IMMUNOLOGICAL SYNAPSE; LINEAGE COMMITMENT; CELL-DIVISION; DIFFERENTIATION; KINASE; EXPRESSION; EFFECTOR; GAMMA; CD4; ITK;
D O I
10.1016/j.immuni.2011.03.017
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:492 / 504
页数:13
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