Cell Death and Survival Pathways Involving ATM Protein Kinase

Abstract

Cell death is the ultimate form of cellular dysfunction, and is induced by a wide range of stresses including genotoxic stresses. During genotoxic stress, two opposite cellular reactions, cellular protection through DNA repair and elimination of damaged cells by the induction of cell death, can occur in both separate and simultaneous manners. ATM (ataxia telangiectasia mutated) kinase (hereafter referred to as ATM) is a protein kinase that plays central roles in the induction of cell death during genotoxic stresses. It has long been considered that ATM mediates DNA damage-induced cell death through inducing apoptosis. However, recent research progress in cell death modality is now revealing ATM-dependent cell death pathways that consist of not only apoptosis but also necroptosis, ferroptosis, and dysfunction of autophagy, a cellular survival mechanism. In this short review, we intend to provide a brief outline of cell death mechanisms in which ATM is involved, with emphasis on pathways other than apoptosis.

Molecular Mechanism and Application of Somatic Cell Cloning in Mammals

“…The most common procedure is a relatively low-invasive method of SCNT based on the fusion of cytoplast-nuclear donor cell couplets that is induced by electric pulses [34,[97][98][99][100][101] (Table 1). An alternative reconstruction method is a much more invasive microsurgical procedure, in which whole nuclear donor cells [102,103] or somatic-cell-derived karyoplasts [29,44,82,104,105] are microinjected directly into the cytoplasm of enucleated oocytes (Table 1). The karyoplast is a live membrane-bound structure formed as a result of mechanically induced lysis of the whole somatic cell.…”

“…The karyoplast is a live membrane-bound structure formed as a result of mechanically induced lysis of the whole somatic cell. It contains the interphase cell nucleus or metaphase chromosomes that are surrounded only by a thin layer of the perinuclear cytoplasm (the so-called perikaryon) [27,[105][106][107][108].…”

“…There are several species-specific epigenetic factors present in the oocyte cytoplasm that may contribute to nuclear-cytoplasmic incompatibilities either immediately after somatic cell nuclear transfer or at later stages of cloned embryo development [105,136,169,170]. In turn, this potential lack of coordination in the interactions of nuclear and cytosolic factors of cybrid cloned zygotes is probably one of the reasons for the limited practical application of the somatic cell cloning technique.…”

“…Such cloned offspring exhibits a degree of variation/incompatibility with regard to phenotypic traits determined by cytoplasmic (extranuclear) inheritance. The latter is dependent on the mitochondrial genotype known as the mitotype [105,157,159,160,167].…”

Bleomycin induced EBV-specific gastric epithelial cell death is enhanced by LMP2A

“…DDR induces phosphorylation of ataxia-telangiectasia mutated (ATM), enhances expression of histone H2AX phosphorylated on Ser193 (γH2AX), and mediates DNA damage checkpoint protein 1 (5)(6)(7). These proteins induce p53 and activate caspase-3, -6, and -7, resulting in the induction of apoptosis (8). When EBV infection causes DNA damage, ATM is activated as a part of the DDR machinery of the host cell.…”