The linker histone H1.2 is an intermediate in the apoptotic response to cytokine deprivation in T-effectors

Garg, Manoj and Perumalsamy, L. R. and Shivashankar, G. V. and Sarin, A. (2014) The linker histone H1.2 is an intermediate in the apoptotic response to cytokine deprivation in T-effectors. International Journal of Cell Biology. ISSN 1687-8876

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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.

Item Type: Article
Uncontrolled Keywords: article, priority journal, controlled study, nonhuman, unclassified drug, cell protection, RNA interference, animal cell, mouse, protein expression, apoptosis, signal transduction, cell structure, cell damage, protein function, membrane damage, cytokine, molecular dynamics, mitochondrial membrane potential, mitochondrial membrane, protein Bak, cytokine production, cellular distribution, cytokine deprivation, cytokine response, cytoplasm, effector cell, histone H1, histone H1.2, leptomycin B, outer membrane, protein depletion, protein localization, stress activated protein kinase, tissue metabolism
Subjects: B Life Science > Biotechnology
Divisions: Department of > Biotechnology
Depositing User: Arshiya Kousar Library Assistant
Date Deposited: 04 Sep 2019 09:55
Last Modified: 20 Jul 2022 05:53

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