The C-terminal domain (CTD) in linker histones antagonizes anti-apoptotic proteins to modulate apoptotic outcomes at the mitochondrion

Garg, Manoj and Ramdas, N. and Vijayalakshmi, M. and Shivashankar, G. V. and Sarin, A. (2014) The C-terminal domain (CTD) in linker histones antagonizes anti-apoptotic proteins to modulate apoptotic outcomes at the mitochondrion. Cell Death and Disease, 5. pp. 1-10.

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The loss of mitochondrial integrity as a consequence of apoptogenic complexes formed on the outer membrane constitutes a key step in controlling progression of apoptotic cascades. Here, we show that multiple members of the linker histone (LH) family of proteins modify apoptotic cascades initiated by the Bcl-2 protein Bak, and impart resistance to its endogenous antagonist Bcl-xL. Our experiments reveal apoptogenic capabilities equivalent to those documented for H1.2 in H1.1 and H1.3 isoforms. Deletion mutants of H1.2 and site-directed mutagenesis of H1.1 and H1.2 implicated the C-terminal domain in apoptogenic activity. In this context, disruption of protein kinase-C activity using chemical inhibitors, dominant-negative approaches and RNA interference coupled with site-directed modifications in H1.1, identified the protein kinase-Cβ1 isoform as a repressor of H1.1/H1.3 apoptogenic activity. Finally, a H1.2 C-terminal tail recombinant attenuated Bcl-xl inhibition of Bak-induced apoptosis, suggesting that the C-terminal domain was necessary and sufficient for apoptogenic functions. Thus, integration with apoptotic intermediates (via C-terminal tail interactions) may constitute a more generalized function of LH isoforms in apoptotic cascades.

Item Type: Article
Additional Information: Unmapped bibliographic data: PY - 2014/02/13/online [EPrints field already has value set] M3 - Original Article [Field not mapped to EPrints] JA - Cell Death Dis [Field not mapped to EPrints] L3 - 10.1038/cddis.2014.20 [Field not mapped to EPrints]
Uncontrolled Keywords: apoptosis, Bak, H1.2-CTD, linker histone, PKC
Subjects: Agriculture Biological Sciences > Biotechnology
University of Mysore > PG Campuses > Manasagangotri, Mysore > Agriculture Biological Sciences > Biotechnology
Divisions: PG Campuses > Manasagangotri, Mysore > Biotechnology
Depositing User: Praveen Kumari B.L
Date Deposited: 14 Jul 2014 07:00
Last Modified: 03 Oct 2015 04:50

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