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International Journal of Cell Biology
Volume 2014 (2014), Article ID 674753, 11 pages
Research Article

The Linker Histone H1.2 Is an Intermediate in the Apoptotic Response to Cytokine Deprivation in T-Effectors

1National Centre for Biological Sciences, Bellary Road, Bangalore, Karnataka 560065, India
2Department of Biotechnology, Mysore University, Mysore, Karnataka 570005, India
3Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India
4Mechanobiology Institute, National University of Singapore, Singapore 117411

Received 3 November 2013; Revised 3 January 2014; Accepted 5 January 2014; Published 13 February 2014

Academic Editor: Claudia Giampietri

Copyright © 2014 Megha Garg et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Tissue homeostasis is a dynamic process involving proliferation and the removal of redundant or damaged cells. This is exemplified in the coordinated deletion—triggered by limiting trophic factors/cytokines in the extracellular milieu—of differentiated T cells overproduced during the mammalian immune response. However, mechanisms by which extracellular cues are perceived and transduced as apoptotic triggers remain incompletely understood. T-effectors are dependent on cytokines for survival and undergo apoptosis following cytokine withdrawal. Here we report that leptomycin B (LMB), an inhibitor of nuclear export machinery, protected T-effectors from apoptosis implicating a nuclear intermediate in the apoptotic pathway. Evidence is presented that the linker histone H1.2 localizes to the cytoplasm, by a mechanism sensitive to regulation by LMB, to activate apoptotic signaling culminating in nuclear and mitochondrial damage in T-effectors in response to cytokine deprivation. H1.2 is detected in a complex with the proapoptotic mitochondrial resident Bak and its subcellular localization regulated by Jun-N-terminal kinase (JNK), an intermediate in the apoptotic cascade in T-effectors. These data suggest that metabolic stressors may impinge on H1.2 dynamics favoring its activity at the mitochondrion, thereby functioning as a molecular switch for T-effector apoptosis.