Identification of DAPK as a scaffold protein for the LIMK/cofilin complex in TNF-induced apoptosis

Ivanovska J, Tregubova A, Mahadevan V, Chakilam S, Gandesiri M, Benderska N, Ettle B, Hartmann A, Söder S, Ziesche E, Fischer T, Lautscham L, Fabry B, Segerer G, Gohla A, Schneider-Stock R (2013)

Publication Type: Journal article

Publication year: 2013

Journal

Original Authors: Ivanovska J, Tregubova A, Mahadevan V, Chakilam S, Gandesiri M, Benderska N, Ettle B, Hartmann A, Söder S, Ziesché E, Fischer T, Lautscham L, Fabry B, Segerer G, Gohla A, Schneider-Stock R

Publisher: Elsevier

DOI: 10.1016/j.biocel.2013.05.013

Abstract

The role of cytoskeleton-associated proteins during TNF-induced apoptosis is not fully understood. A potential candidate kinase that might connect TNF signalling to actin reorganization is the death-associated protein kinase (DAPK). To identify new DAPK interaction partners in TNF-induced apoptosis, we performed a peptide array screen. We show that TNF-treatment enhanced the phosphorylation of LIMK at threonine508 and its downstream target cofilin at serine3 (p-cofilin(Ser3)). Modulation of DAPK activity and expression by DAPK inhibitor treatment, siRNA knockdown, and overexpression affected the phosphorylation of both proteins. We propose a 3D structural model where DAPK functions as a scaffold for the LIMK/cofilin complex and triggers a closer interaction of both proteins under TNF stimulation. Upon TNF a striking redistribution of LIMK, DAPK, and cofilin to the perinuclear compartment was observed. The pro-apoptotic DAPK/LIMK/cofilin multiprotein complex was abrogated in detached cells, indicating that its signaling was no longer needed if cells committed to apoptosis. P-cofilin(Ser3) was strongly accumulated in cells with condensed chromatin, pronounced membrane blebs and Annexin V up-regulation. From studying different cofilin(Ser3) mutants we suggest that p-cofilin(Ser3) is an indicator of TNF-induced apoptosis. Collectively, our findings identify a novel molecular cytoskeleton-associated mechanism in TNF-induced DAPK-dependent apoptosis.

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Involved external institutions

Julius-Maximilians-Universität Würzburg Germany (DE) Shanmugha Arts, Science, Technology & Research Academy (SASTRA University) India (IN) Otto-von-Guericke-Universität Magdeburg Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE)

How to cite

APA:

Ivanovska, J., Tregubova, A., Mahadevan, V., Chakilam, S., Gandesiri, M., Benderska, N.,... Schneider-Stock, R. (2013). Identification of DAPK as a scaffold protein for the LIMK/cofilin complex in TNF-induced apoptosis. International Journal of Biochemistry and Cell Biology. https://dx.doi.org/10.1016/j.biocel.2013.05.013

MLA:

Ivanovska, Jelena, et al. "Identification of DAPK as a scaffold protein for the LIMK/cofilin complex in TNF-induced apoptosis." International Journal of Biochemistry and Cell Biology (2013).

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