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Molecular and Cellular Biology, September 2001, p. 5797-5805, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5797-5805.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

c-myb Transcription Is Activated by Protein Kinase B (PKB) following Interleukin 2 Stimulation of T Cells and Is Required for PKB-Mediated Protection from Apoptosis

Angus Lauder,dagger Andres Castellanos, and Kathleen Weston*

CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, London SW3 6JB, United Kingdom

Received 11 September 2000/Returned for modification 3 November 2000/Accepted 7 June 2001

During T-cell activation, c-Myb is induced upon interleukin 2 (IL-2) stimulation and is required for correct proliferation of cells. In this paper, we provide evidence that IL-2-mediated induction of the c-myb gene occurs via the phosphoinositide 3-kinase (PI3K) signaling pathway, that protein kinase B (PKB) is the principal transducer of this signal, and that activation of the c-myb promoter can be abolished by deletion of conserved E2F and NF-kappa B binding sites. We show that Myb is required to protect activated peripheral T cells from bcl-2-independent apoptosis and that overexpression of oncogenic v-Myb is antiapoptotic. Overexpression of a Myb dominant-negative transgene abrogates PKB-mediated protection from apoptosis. Taken together, these results suggest that induction of c-myb transcription is an important downstream event for PKB-mediated protection of T cells from programmed cell death.

* Corresponding author. Mailing address: CRC Centre for Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Rd., London SW3 6JB, United Kingdom. Phone: 44 20 7878 3846. Fax: 44 20 7352 3299. E-mail: kathy{at}icr.ac.uk.

dagger Present address: MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom.

Molecular and Cellular Biology, September 2001, p. 5797-5805, Vol. 21, No. 17
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.17.5797-5805.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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