Please use this identifier to cite or link to this item: https://doi.org/10.1038/cddis.2014.20
Title: The C-terminal domain (CTD) in linker histones antagonizes anti-apoptotic proteins to modulate apoptotic outcomes at the mitochondrion
Authors: Garg, M.
Ramdas, N.
Vijayalakshmi, M.
Shivashankar, G.V. 
Sarin, A.
Keywords: apoptosis
Bak
H1.2-CTD
linker histone
PKC
Issue Date: Feb-2014
Citation: Garg, M., Ramdas, N., Vijayalakshmi, M., Shivashankar, G.V., Sarin, A. (2014-02). The C-terminal domain (CTD) in linker histones antagonizes anti-apoptotic proteins to modulate apoptotic outcomes at the mitochondrion. Cell Death and Disease 5 (2) : -. ScholarBank@NUS Repository. https://doi.org/10.1038/cddis.2014.20
Abstract: 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-Cb1 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. © 2014 Macmillan Publishers Limited.
Source Title: Cell Death and Disease
URI: http://scholarbank.nus.edu.sg/handle/10635/126622
ISSN: 20414889
DOI: 10.1038/cddis.2014.20
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