Molecular mechanisms of cellular transformation by HTLV-1 Tax

Ralph Grassmann; Mordechai Aboud; Kuan Teh Jeang

doi:10.1038/sj.onc.1208978

Molecular mechanisms of cellular transformation by HTLV-1 Tax

Ralph Grassmann, Mordechai Aboud, Kuan Teh Jeang

The Shraga Segal Department of Microbiology, Immunology and Genetics

Research output: Contribution to journal › Article › peer-review

350 Scopus citations

Abstract

The HTLV Tax protein is crucial for viral replication and for initiating malignant transformation leading to the development of adult T-cell leukemia. Tax has been shown to be oncogenic, since it transforms and immortalizes rodent fibroblasts and human T-lymphocytes. Through CREB, NF-κB and SRF pathways Tax transactivates cellular promoters including those of cytokines (IL-13, IL-15), cytokine receptors (IL-2Rα) and costimulatory surface receptors (OX40/OX40L) leading to upregulated protein expression and activated signaling cascades (e.g. Jak/STAT, PI3Kinase, JNK). Tax also stimulates cell growth by direct binding to cyclin-dependent kinase holenzymes and/or inactivating tumor suppressors (e.g. p53, DLG). Moreover, Tax silences cellular checkpoints, which guard against DNA structural damage and chromosomal missegregation, thereby favoring the manifestation of a mutator phenotype in cells.

Original language	English
Pages (from-to)	5976-5985
Number of pages	10
Journal	Oncogene
Volume	24
Issue number	39
DOIs	https://doi.org/10.1038/sj.onc.1208978
State	Published - 5 Sep 2005

Keywords

ATLL apoptosis
Cell cycle
HTLV
Immortalization
Leukemia
T-lymphocyte
Tax
Transformation

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/sj.onc.1208978

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title = "Molecular mechanisms of cellular transformation by HTLV-1 Tax",

abstract = "The HTLV Tax protein is crucial for viral replication and for initiating malignant transformation leading to the development of adult T-cell leukemia. Tax has been shown to be oncogenic, since it transforms and immortalizes rodent fibroblasts and human T-lymphocytes. Through CREB, NF-κB and SRF pathways Tax transactivates cellular promoters including those of cytokines (IL-13, IL-15), cytokine receptors (IL-2Rα) and costimulatory surface receptors (OX40/OX40L) leading to upregulated protein expression and activated signaling cascades (e.g. Jak/STAT, PI3Kinase, JNK). Tax also stimulates cell growth by direct binding to cyclin-dependent kinase holenzymes and/or inactivating tumor suppressors (e.g. p53, DLG). Moreover, Tax silences cellular checkpoints, which guard against DNA structural damage and chromosomal missegregation, thereby favoring the manifestation of a mutator phenotype in cells.",

keywords = "ATLL apoptosis, Cell cycle, HTLV, Immortalization, Leukemia, T-lymphocyte, Tax, Transformation",

author = "Ralph Grassmann and Mordechai Aboud and Jeang, {Kuan Teh}",

note = "Funding Information: This work was supported in part by DFG (Grant SFB466-TPC3) and Wilhelm Sander-Stiftung (to RG). We thank Anthony Elmo for assistance with manuscript preparation.",

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AU - Grassmann, Ralph

AU - Aboud, Mordechai

AU - Jeang, Kuan Teh

N1 - Funding Information: This work was supported in part by DFG (Grant SFB466-TPC3) and Wilhelm Sander-Stiftung (to RG). We thank Anthony Elmo for assistance with manuscript preparation.

PY - 2005/9/5

Y1 - 2005/9/5

N2 - The HTLV Tax protein is crucial for viral replication and for initiating malignant transformation leading to the development of adult T-cell leukemia. Tax has been shown to be oncogenic, since it transforms and immortalizes rodent fibroblasts and human T-lymphocytes. Through CREB, NF-κB and SRF pathways Tax transactivates cellular promoters including those of cytokines (IL-13, IL-15), cytokine receptors (IL-2Rα) and costimulatory surface receptors (OX40/OX40L) leading to upregulated protein expression and activated signaling cascades (e.g. Jak/STAT, PI3Kinase, JNK). Tax also stimulates cell growth by direct binding to cyclin-dependent kinase holenzymes and/or inactivating tumor suppressors (e.g. p53, DLG). Moreover, Tax silences cellular checkpoints, which guard against DNA structural damage and chromosomal missegregation, thereby favoring the manifestation of a mutator phenotype in cells.

AB - The HTLV Tax protein is crucial for viral replication and for initiating malignant transformation leading to the development of adult T-cell leukemia. Tax has been shown to be oncogenic, since it transforms and immortalizes rodent fibroblasts and human T-lymphocytes. Through CREB, NF-κB and SRF pathways Tax transactivates cellular promoters including those of cytokines (IL-13, IL-15), cytokine receptors (IL-2Rα) and costimulatory surface receptors (OX40/OX40L) leading to upregulated protein expression and activated signaling cascades (e.g. Jak/STAT, PI3Kinase, JNK). Tax also stimulates cell growth by direct binding to cyclin-dependent kinase holenzymes and/or inactivating tumor suppressors (e.g. p53, DLG). Moreover, Tax silences cellular checkpoints, which guard against DNA structural damage and chromosomal missegregation, thereby favoring the manifestation of a mutator phenotype in cells.

KW - ATLL apoptosis

KW - Cell cycle

KW - HTLV

KW - Immortalization

KW - Leukemia

KW - T-lymphocyte

KW - Tax

KW - Transformation

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ER -

Molecular mechanisms of cellular transformation by HTLV-1 Tax

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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