Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Aug;45(8):1720-9.
doi: 10.1016/j.biocel.2013.05.013. Epub 2013 May 20.

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

Jelena Ivanovska  1 , Alexandra Tregubova, Vijayalakshmi Mahadevan, Saritha Chakilam, Muktheshwar Gandesiri, Natalya Benderska, Benjamin Ettle, Arndt Hartmann, Stephan Söder, Elisabeth Ziesché, Thomas Fischer, Lena Lautscham, Ben Fabry, Gabriela Segerer, Antje Gohla, Regine Schneider-Stock
Affiliations

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

Jelena Ivanovska et al. Int J Biochem Cell Biol. 2013 Aug.

Abstract

The role of cytoskeleton-associated proteins during TNF-induced apoptosis is not fully understood. A potential candidate kinase that might connect TNF signaling 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.

Keywords: Apoptosis; Cofilin; DAPK; LIMK; TNF.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources