Loss of adenomatous polyposis coli gene function disrupts thymic development

Fotini Gounari, Rui Chang, Janet Cowan, Zhuyan Guo, Marei Dose, Elias Gounaris, Khashayarsha Khazaie

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Loss of the adenomatous polyposis coli (APC) protein is a common initiating event in colon cancer. Here we show that thymocyte-specific loss of APC deregulated β-catenin signaling and suppressed Notch-dependent transcription. These events promoted the proliferation of cells of the double-negative 3 and 4 stages and reduced rearrangements between the variable, diversity and joining regions of the gene encoding T cell receptor (TCR) β, encouraging developmental progression of aberrant thymocytes lacking pre-TCR and αβ TCR. Simultaneously, the loss of APC prolonged the mitotic metaphase-to-anaphase checkpoint and impaired chromosome segregation, blocking development beyond the double-negative 4 stage. The result was extensive thymic atrophy and increased frequencies of thymocytes with chromosomal abnormalities. Thus, loss of APC in immature thymocytes has consequences distinct from those of deregulation of β-catenin signaling and is essential for T cell differentiation.

Original languageEnglish (US)
Pages (from-to)800-809
Number of pages10
JournalNature Immunology
Volume6
Issue number8
DOIs
StatePublished - Aug 2005
Externally publishedYes

Fingerprint

APC Genes
Thymocytes
Adenomatous Polyposis Coli
Catenins
T-Cell Antigen Receptor
Adenomatous Polyposis Coli Protein
T-Cell Receptor Genes
Chromosome Segregation
Anaphase
Metaphase
Chromosome Aberrations
Colonic Neoplasms
Atrophy
Cell Differentiation
Cell Proliferation
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Gounari, F., Chang, R., Cowan, J., Guo, Z., Dose, M., Gounaris, E., & Khazaie, K. (2005). Loss of adenomatous polyposis coli gene function disrupts thymic development. Nature Immunology, 6(8), 800-809. https://doi.org/10.1038/ni1228

Loss of adenomatous polyposis coli gene function disrupts thymic development. / Gounari, Fotini; Chang, Rui; Cowan, Janet; Guo, Zhuyan; Dose, Marei; Gounaris, Elias; Khazaie, Khashayarsha.

In: Nature Immunology, Vol. 6, No. 8, 08.2005, p. 800-809.

Research output: Contribution to journalArticle

Gounari, F, Chang, R, Cowan, J, Guo, Z, Dose, M, Gounaris, E & Khazaie, K 2005, 'Loss of adenomatous polyposis coli gene function disrupts thymic development', Nature Immunology, vol. 6, no. 8, pp. 800-809. https://doi.org/10.1038/ni1228
Gounari F, Chang R, Cowan J, Guo Z, Dose M, Gounaris E et al. Loss of adenomatous polyposis coli gene function disrupts thymic development. Nature Immunology. 2005 Aug;6(8):800-809. https://doi.org/10.1038/ni1228
Gounari, Fotini ; Chang, Rui ; Cowan, Janet ; Guo, Zhuyan ; Dose, Marei ; Gounaris, Elias ; Khazaie, Khashayarsha. / Loss of adenomatous polyposis coli gene function disrupts thymic development. In: Nature Immunology. 2005 ; Vol. 6, No. 8. pp. 800-809.
@article{ec7e7697e2294c51a09146780139519d,
title = "Loss of adenomatous polyposis coli gene function disrupts thymic development",
abstract = "Loss of the adenomatous polyposis coli (APC) protein is a common initiating event in colon cancer. Here we show that thymocyte-specific loss of APC deregulated β-catenin signaling and suppressed Notch-dependent transcription. These events promoted the proliferation of cells of the double-negative 3 and 4 stages and reduced rearrangements between the variable, diversity and joining regions of the gene encoding T cell receptor (TCR) β, encouraging developmental progression of aberrant thymocytes lacking pre-TCR and αβ TCR. Simultaneously, the loss of APC prolonged the mitotic metaphase-to-anaphase checkpoint and impaired chromosome segregation, blocking development beyond the double-negative 4 stage. The result was extensive thymic atrophy and increased frequencies of thymocytes with chromosomal abnormalities. Thus, loss of APC in immature thymocytes has consequences distinct from those of deregulation of β-catenin signaling and is essential for T cell differentiation.",
author = "Fotini Gounari and Rui Chang and Janet Cowan and Zhuyan Guo and Marei Dose and Elias Gounaris and Khashayarsha Khazaie",
year = "2005",
month = "8",
doi = "10.1038/ni1228",
language = "English (US)",
volume = "6",
pages = "800--809",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Loss of adenomatous polyposis coli gene function disrupts thymic development

AU - Gounari, Fotini

AU - Chang, Rui

AU - Cowan, Janet

AU - Guo, Zhuyan

AU - Dose, Marei

AU - Gounaris, Elias

AU - Khazaie, Khashayarsha

PY - 2005/8

Y1 - 2005/8

N2 - Loss of the adenomatous polyposis coli (APC) protein is a common initiating event in colon cancer. Here we show that thymocyte-specific loss of APC deregulated β-catenin signaling and suppressed Notch-dependent transcription. These events promoted the proliferation of cells of the double-negative 3 and 4 stages and reduced rearrangements between the variable, diversity and joining regions of the gene encoding T cell receptor (TCR) β, encouraging developmental progression of aberrant thymocytes lacking pre-TCR and αβ TCR. Simultaneously, the loss of APC prolonged the mitotic metaphase-to-anaphase checkpoint and impaired chromosome segregation, blocking development beyond the double-negative 4 stage. The result was extensive thymic atrophy and increased frequencies of thymocytes with chromosomal abnormalities. Thus, loss of APC in immature thymocytes has consequences distinct from those of deregulation of β-catenin signaling and is essential for T cell differentiation.

AB - Loss of the adenomatous polyposis coli (APC) protein is a common initiating event in colon cancer. Here we show that thymocyte-specific loss of APC deregulated β-catenin signaling and suppressed Notch-dependent transcription. These events promoted the proliferation of cells of the double-negative 3 and 4 stages and reduced rearrangements between the variable, diversity and joining regions of the gene encoding T cell receptor (TCR) β, encouraging developmental progression of aberrant thymocytes lacking pre-TCR and αβ TCR. Simultaneously, the loss of APC prolonged the mitotic metaphase-to-anaphase checkpoint and impaired chromosome segregation, blocking development beyond the double-negative 4 stage. The result was extensive thymic atrophy and increased frequencies of thymocytes with chromosomal abnormalities. Thus, loss of APC in immature thymocytes has consequences distinct from those of deregulation of β-catenin signaling and is essential for T cell differentiation.

UR - http://www.scopus.com/inward/record.url?scp=23944472219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23944472219&partnerID=8YFLogxK

U2 - 10.1038/ni1228

DO - 10.1038/ni1228

M3 - Article

C2 - 16025118

AN - SCOPUS:23944472219

VL - 6

SP - 800

EP - 809

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 8

ER -