Home LiteratureArticle Details
PMID: 21497118 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

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

Immunity ·Vol. 34 ·No. 4 ·2011-04-22 ·Pages 492-504

Chang JT, Ciocca ML, Kinjyo I, Palanivel VR, McClurkin CE, Dejong CS, Mooney EC, Kim JS, Steinel NC, Oliaro J, Yin CC, Florea BI, Overkleeft HS, Berg LJ, Russell SM, Koretzky GA, Jordan MS, Reiner SL

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.

MeSH Terms
Animals Cell Polarity Cells, Cultured Mice Mice, Inbred C57BL Mitosis Phosphorylation Proteasome Endopeptidase Complex/metabolism T-Box Domain Proteins/immunology,metabolism T-Lymphocytes/cytology,enzymology,immunology
Chemicals
T-Box Domain Proteins T-box transcription factor TBX21 Proteasome Endopeptidase Complex
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Chang John T
Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. changj@ucsd.edu
Ciocca Maria L
Kinjyo Ichiko
Palanivel Vikram R
McClurkin Courtney E
Dejong Caitlin S
Mooney Erin C
Kim Jiyeon S
Steinel Natalie C
Oliaro Jane
Yin Catherine C
Florea Bogdan I
Overkleeft Herman S
Berg Leslie J
Russell Sarah M
Koretzky Gary A
Jordan Martha S
Reiner Steven L
References (50)
50 references, click to expand
  1. One naive T cell, multiple fates in CD8+ T cell differentiation.
    J Exp Med. 2010 Jun 7;207(6):1235-46 PMID: 20479114
  2. Asymmetric cell division of T cells upon antigen presentation uses multiple conserved mechanisms.
    J Immunol. 2010 Jul 1;185(1):367-75 PMID: 20530266
  3. Subcellular dynamics of T cell immunological synapses and kinapses in lymph nodes.
    Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3675-80 PMID: 20133676
  4. Asymmetric mitosis: Unequal segregation of proteins destined for degradation.
    Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7732-7 PMID: 18511557
  5. Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction.
    Nat Immunol. 2002 Jul;3(7):652-8 PMID: 12055627
  6. Novel chromophores and buried charges control color in mFruits.
    Biochemistry. 2006 Aug 15;45(32):9639-47 PMID: 16893165
  7. T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells.
    Nat Immunol. 2002 Jun;3(6):549-57 PMID: 12006974
  8. Regulation of a late phase of T cell polarity and effector functions by Crtam.
    Cell. 2008 Mar 7;132(5):846-59 PMID: 18329370
  9. itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2.
    Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11194-8 PMID: 1280821
  10. A method for prolonged imaging of motile lymphocytes.
    Immunol Cell Biol. 2009 Feb;87(2):154-8 PMID: 18982018
  11. A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection.
    Immunity. 2009 Aug 21;31(2):309-20 PMID: 19664943
  12. A role for the immunological synapse in lineage commitment of CD4 lymphocytes.
    Nature. 2004 Sep 30;431(7008):527-32 PMID: 15386021
  13. Regulation of planar cell polarity by Smurf ubiquitin ligases.
    Cell. 2009 Apr 17;137(2):295-307 PMID: 19379695
  14. Asymmetric T lymphocyte division in the initiation of adaptive immune responses.
    Science. 2007 Mar 23;315(5819):1687-91 PMID: 17332376
  15. A network of PDZ-containing proteins regulates T cell polarity and morphology during migration and immunological synapse formation.
    Immunity. 2005 Jun;22(6):737-48 PMID: 15963788
  16. Complementation in trans of altered thymocyte development in mice expressing mutant forms of the adaptor molecule SLP76.
    Immunity. 2008 Mar;28(3):359-69 PMID: 18342008
  17. Activity-based profiling reveals reactivity of the murine thymoproteasome-specific subunit beta5t.
    Chem Biol. 2010 Aug 27;17(8):795-801 PMID: 20797608
  18. Mutation of Tec family kinases alters T helper cell differentiation.
    Nat Immunol. 2001 Dec;2(12):1183-8 PMID: 11702066
  19. Cutting edge: in vivo identification of TCR redistribution and polarized IL-2 production by naive CD4 T cells.
    J Immunol. 2001 Apr 1;166(7):4278-81 PMID: 11254679
  20. Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor.
    Immunity. 2007 Aug;27(2):281-95 PMID: 17723218
  21. Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin.
    Nat Immunol. 2005 Dec;6(12):1236-44 PMID: 16273099
  22. Three-dimensional segregation of supramolecular activation clusters in T cells.
    Nature. 1998 Sep 3;395(6697):82-6 PMID: 9738502
  23. T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells.
    J Exp Med. 1998 May 18;187(10):1721-7 PMID: 9584150
  24. Dissecting T cell lineage relationships by cellular barcoding.
    J Exp Med. 2008 Sep 29;205(10):2309-18 PMID: 18809713
  25. Centrosome polarization delivers secretory granules to the immunological synapse.
    Nature. 2006 Sep 28;443(7110):462-5 PMID: 17006514
  26. Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells.
    J Exp Med. 2007 Sep 3;204(9):2015-21 PMID: 17698591
  27. Mechanisms of asymmetric stem cell division.
    Cell. 2008 Feb 22;132(4):583-97 PMID: 18295577
  28. Differential expression of interleukin-17A and -17F is coupled to T cell receptor signaling via inducible T cell kinase.
    Immunity. 2009 Oct 16;31(4):587-97 PMID: 19818650
  29. Transcriptional repressor Blimp-1 promotes CD8(+) T cell terminal differentiation and represses the acquisition of central memory T cell properties.
    Immunity. 2009 Aug 21;31(2):296-308 PMID: 19664941
  30. Asymmetric cell divisions promote stratification and differentiation of mammalian skin.
    Nature. 2005 Sep 8;437(7056):275-80 PMID: 16094321
  31. In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain.
    J Exp Med. 2006 Sep 4;203(9):2095-107 PMID: 16923851
  32. Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics.
    J Exp Med. 2010 Nov 22;207(12):2733-49 PMID: 21041455
  33. Control of T helper 2 cell function and allergic airway inflammation by PKCzeta.
    Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9866-71 PMID: 15987782
  34. T cells use two directionally distinct pathways for cytokine secretion.
    Nat Immunol. 2006 Mar;7(3):247-55 PMID: 16444260
  35. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet.
    Science. 2002 Jan 11;295(5553):336-8 PMID: 11786643
  36. Impaired NFATc translocation and failure of Th2 development in Itk-deficient CD4+ T cells.
    Immunity. 1999 Oct;11(4):399-409 PMID: 10549622
  37. Visualizing the functional diversification of CD8+ T cell responses in lymph nodes.
    Immunity. 2010 Sep 24;33(3):412-23 PMID: 20850354
  38. Blimp-1 transcription factor is required for the differentiation of effector CD8(+) T cells and memory responses.
    Immunity. 2009 Aug 21;31(2):283-95 PMID: 19664942
  39. T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells.
    Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15137-42 PMID: 11752460
  40. Protein kinase C zeta is required for epidermal growth factor-induced chemotaxis of human breast cancer cells.
    Cancer Res. 2005 Feb 15;65(4):1433-41 PMID: 15735031
  41. T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt.
    Nat Immunol. 2011 Jan;12(1):96-104 PMID: 21151104
  42. The Tec family tyrosine kinases Itk and Rlk regulate the development of conventional CD8+ T cells.
    Immunity. 2006 Jul;25(1):79-91 PMID: 16860759
  43. T-cell receptor signals direct the composition and function of the memory CD8+ T-cell pool.
    Blood. 2010 Dec 16;116(25):5548-59 PMID: 20847203
  44. Signalling through TEC kinases regulates conventional versus innate CD8(+) T-cell development.
    Nat Rev Immunol. 2007 Jun;7(6):479-85 PMID: 17479128
  45. A novel transcription factor, T-bet, directs Th1 lineage commitment.
    Cell. 2000 Mar 17;100(6):655-69 PMID: 10761931
  46. T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3.
    Science. 2005 Jan 21;307(5708):430-3 PMID: 15662016
  47. Dare to be different: asymmetric cell division in Drosophila, C. elegans and vertebrates.
    Curr Biol. 2004 Aug 24;14(16):R674-85 PMID: 15324689
  48. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells.
    Science. 2002 Jan 11;295(5553):338-42 PMID: 11786644
  49. Displacement of sequence-specific transcription factors from mitotic chromatin.
    Cell. 1995 Oct 6;83(1):29-38 PMID: 7553870
  50. A single naive CD8+ T cell precursor can develop into diverse effector and memory subsets.
    Immunity. 2007 Dec;27(6):985-97 PMID: 18082432
Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
Published
2011-04-22
Epub
2011-00-14
Pages
492-504
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3088519
Subset
IM
Grants
NIAMS NIH HHS · K01 AR052802 · United States
NIAID NIH HHS · R01 AI037584 · United States
NCI NIH HHS · P01 CA093615-07 · United States
NIAID NIH HHS · R01 AI046564-05 · United States
NCI NIH HHS · P01 CA093615-06 · United States
NIDDK NIH HHS · K08 DK080949-03 · United States
NIAID NIH HHS · R01 AI042370 · United States
NIAID NIH HHS · R01 AI046564 · United States
NIAID NIH HHS · R01 AI076458-03 · United States
NIGMS NIH HHS · GM053256 · United States
NIAID NIH HHS · AI061699 · United States
NIAID NIH HHS · R01 AI076458 · United States
NIAMS NIH HHS · K01 AR052802-04 · United States
NIAID NIH HHS · R56 AI076458 · United States
NIAID NIH HHS · R01 AI042370-13 · United States
NIAID NIH HHS · AI37584 · United States
NIAID NIH HHS · T32 AI055428 · United States
NIDDK NIH HHS · R24 DK080506 · United States
NIDDK NIH HHS · DK80506 · United States
NCI NIH HHS · P01 CA093615 · United States
NIAID NIH HHS · R01 AI076458-04 · United States
NIGMS NIH HHS · R37 GM053256-15 · United States
NICHD NIH HHS · T32 HD007516 · United States
NIDDK NIH HHS · K08 DK080949 · United States
NIGMS NIH HHS · R01 GM053256 · United States
NIAID NIH HHS · R01 AI042370-14 · United States
NICHD NIH HHS · T32HD007516 · United States
NIDDK NIH HHS · K08 DK080949-04 · United States
NIAID NIH HHS · R01 AI061699-05 · United States
NIAID NIH HHS · R01 AI076458-05 · United States
NIDDK NIH HHS · DK080949 · United States
NIAID NIH HHS · AI46564 · United States
NCI NIH HHS · CA093615 · United States
NIAID NIH HHS · AI076458 · United States
NIAID NIH HHS · R01 AI042370-15 · United States
NIGMS NIH HHS · R37 GM053256-14 · United States
NIAID NIH HHS · R01 AI084987 · United States
NIAID NIH HHS · R01 AI046564-04 · United States
NIGMS NIH HHS · R37 GM053256 · United States
NIDDK NIH HHS · K08 DK080949-05 · United States
NIAMS NIH HHS · AR052802 · United States
NIAMS NIH HHS · K01 AR052802-05 · United States
NIAID NIH HHS · R01 AI061699 · United States
NIAID NIH HHS · AI042370 · United States
NIAID NIH HHS · R01 AI037584-12 · United States
NIAID NIH HHS · R01 AI037584-11A1 · United States
Corrections
CommentIn
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com