title: The linker histone h1.2 is an intermediate in the apoptotic response to cytokine deprivation in T-effectors.
abstract: 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.
authors.affiliation: National Centre for Biological Sciences, Bellary Road, Bangalore, Karnataka 560065, India ; Department of Biotechnology, Mysore University, Mysore, Karnataka 570005, India.
authors.forename: Megha
authors.initials: M
authors.lastname: Garg
authors.affiliation: National Centre for Biological Sciences, Bellary Road, Bangalore, Karnataka 560065, India ; Department of Biotechnology, Indian Institute of Technology Madras, Chennai, Tamil Nadu 600036, India.
authors.forename: Lakshmi R
authors.initials: LR
authors.lastname: Perumalsamy
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: G V
authors.initials: GV
authors.lastname: Shivashankar
authors.affiliation: National Centre for Biological Sciences, Bellary Road, Bangalore, Karnataka 560065, India.
authors.forename: Apurva
authors.identifier: 0000-0003-0851-4818
authors.initials: A
authors.lastname: Sarin