Discovery - University of Dundee - Online Publications

Library & Learning Centre

Tyrosine dephosphorylation is required for Bak activation in apoptosis

Standard

Tyrosine dephosphorylation is required for Bak activation in apoptosis. / Fox, Joanna L.; Ismail, Ferina; Azad, Abul; Ternette, Nicola; Leverrier, Sabrina; Edelmann, Mariola J.; Kessler, Benedikt M.; Leigh, Irene M.; Jackson, Sarah; Storey, Alan.

In: EMBO Journal, Vol. 29, No. 22, 17.11.2010, p. 3853-3868.

Research output: Contribution to journalArticle

Harvard

Fox, JL, Ismail, F, Azad, A, Ternette, N, Leverrier, S, Edelmann, MJ, Kessler, BM, Leigh, IM, Jackson, S & Storey, A 2010, 'Tyrosine dephosphorylation is required for Bak activation in apoptosis' EMBO Journal, vol 29, no. 22, pp. 3853-3868., 10.1038/emboj.2010.244

APA

Fox, J. L., Ismail, F., Azad, A., Ternette, N., Leverrier, S., Edelmann, M. J., ... Storey, A. (2010). Tyrosine dephosphorylation is required for Bak activation in apoptosis. EMBO Journal, 29(22), 3853-3868. 10.1038/emboj.2010.244

Vancouver

Fox JL, Ismail F, Azad A, Ternette N, Leverrier S, Edelmann MJ et al. Tyrosine dephosphorylation is required for Bak activation in apoptosis. EMBO Journal. 2010 Nov 17;29(22):3853-3868. Available from: 10.1038/emboj.2010.244

Author

Fox, Joanna L.; Ismail, Ferina; Azad, Abul; Ternette, Nicola; Leverrier, Sabrina; Edelmann, Mariola J.; Kessler, Benedikt M.; Leigh, Irene M.; Jackson, Sarah; Storey, Alan / Tyrosine dephosphorylation is required for Bak activation in apoptosis.

In: EMBO Journal, Vol. 29, No. 22, 17.11.2010, p. 3853-3868.

Research output: Contribution to journalArticle

Bibtex - Download

@article{cfd4213bbb8e444cb9361d9fabcb4b0b,
title = "Tyrosine dephosphorylation is required for Bak activation in apoptosis",
keywords = "apoptosis, Bak, mitochondria, phosphatase, SIGNAL-REGULATED KINASE, CYTOCHROME-C RELEASE, MITOCHONDRIAL APOPTOSIS, MASS-SPECTROMETRY, OLIGOMERIZES BAK, CELL-DEATH, PROTEIN, BCL-2, PATHWAY, INHIBITION",
author = "Fox, {Joanna L.} and Ferina Ismail and Abul Azad and Nicola Ternette and Sabrina Leverrier and Edelmann, {Mariola J.} and Kessler, {Benedikt M.} and Leigh, {Irene M.} and Sarah Jackson and Alan Storey",
year = "2010",
doi = "10.1038/emboj.2010.244",
volume = "29",
number = "22",
pages = "3853--3868",
journal = "EMBO Journal",
issn = "0261-4189",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Tyrosine dephosphorylation is required for Bak activation in apoptosis

A1 - Fox,Joanna L.

A1 - Ismail,Ferina

A1 - Azad,Abul

A1 - Ternette,Nicola

A1 - Leverrier,Sabrina

A1 - Edelmann,Mariola J.

A1 - Kessler,Benedikt M.

A1 - Leigh,Irene M.

A1 - Jackson,Sarah

A1 - Storey,Alan

AU - Fox,Joanna L.

AU - Ismail,Ferina

AU - Azad,Abul

AU - Ternette,Nicola

AU - Leverrier,Sabrina

AU - Edelmann,Mariola J.

AU - Kessler,Benedikt M.

AU - Leigh,Irene M.

AU - Jackson,Sarah

AU - Storey,Alan

PY - 2010/11/17

Y1 - 2010/11/17

N2 - <p>Activation of the cell-death mediator Bak commits a cell to mitochondrial apoptosis. The initial steps that govern Bak activation are poorly understood. To further clarify these pivotal events, we have investigated whether post-translational modifications of Bak impinge on its activation potential. In this study, we report that on apoptotic stimulation Bak undergoes dephosphorylation at tyrosine residue 108 (Y108), a critical event that is necessary but not sufficient for Bak activation, but is required both for early exposure of the occluded N-terminal domain and multi-merisation. RNA interference (RNAi) screening identified non-receptor tyrosine phosphatases (PTPNs) required for Bak dephosphorylation and apoptotic induction through chemotherapeutic agents. Specifically, modulation of PTPN5 protein expression by siRNA and overexpression directly affected both Bak-Y108 phosphorylation and the initiation of Bak activation. We further show that MEK/ERK signalling directly affects Bak phosphorylation through inhibition of PTPN5 to promote cell survival. We propose a model of Bak activation in which the regulation of Bak dephosphorylation constitutes the initial step in the activation process, which reveals a previously unsuspected mechanism controlling the initiation of mitochondrial apoptosis.</p>

AB - <p>Activation of the cell-death mediator Bak commits a cell to mitochondrial apoptosis. The initial steps that govern Bak activation are poorly understood. To further clarify these pivotal events, we have investigated whether post-translational modifications of Bak impinge on its activation potential. In this study, we report that on apoptotic stimulation Bak undergoes dephosphorylation at tyrosine residue 108 (Y108), a critical event that is necessary but not sufficient for Bak activation, but is required both for early exposure of the occluded N-terminal domain and multi-merisation. RNA interference (RNAi) screening identified non-receptor tyrosine phosphatases (PTPNs) required for Bak dephosphorylation and apoptotic induction through chemotherapeutic agents. Specifically, modulation of PTPN5 protein expression by siRNA and overexpression directly affected both Bak-Y108 phosphorylation and the initiation of Bak activation. We further show that MEK/ERK signalling directly affects Bak phosphorylation through inhibition of PTPN5 to promote cell survival. We propose a model of Bak activation in which the regulation of Bak dephosphorylation constitutes the initial step in the activation process, which reveals a previously unsuspected mechanism controlling the initiation of mitochondrial apoptosis.</p>

KW - apoptosis

KW - Bak

KW - mitochondria

KW - phosphatase

KW - SIGNAL-REGULATED KINASE

KW - CYTOCHROME-C RELEASE

KW - MITOCHONDRIAL APOPTOSIS

KW - MASS-SPECTROMETRY

KW - OLIGOMERIZES BAK

KW - CELL-DEATH

KW - PROTEIN

KW - BCL-2

KW - PATHWAY

KW - INHIBITION

U2 - 10.1038/emboj.2010.244

DO - 10.1038/emboj.2010.244

M1 - Article

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 22

VL - 29

SP - 3853

EP - 3868

ER -

Documents

Library & Learning Centre

Contact | Accessibility | Policy