Apoptosis Induction and Regulation

Abstract

Apoptosis is one of the main modalities of cell death, so important that it has outshined all others that only begin to be rediscovered. Apoptosis is an active, programmed way of cell death, implemented in response to intracellular or extracellular signals. Intracellular signals can originate from DNA lesions, mitosis defects, oxidative stress or other stresses, while extracellular signals correspond to death messages emitted by other cells. Apoptosis leads to the activation of proteases, called caspases, able to hydrolyse the cell constituents independently from the proteasome. Apoptosis plays many fundamental roles during embryology and tissue homoeostasis; to provide only one example, it is responsible for thymus regression during the passage from childhood to adulthood. Many authors have considered apoptosis as the obligate pathway to cell death induced by anticancer drugs, but in many cases it is only a phenotypic consequence, secondary to other mechanisms of drug-induced cell death, which only indirectly involve apoptosis. Apoptosis is often opposed to necrosis, but comparisons can also be made with senescence and mitotic cell death.

We present in this chapter the signalling pathways which lead to the execution of the cell death programme, but we neither describe the techniques that allow to detect or quantify apoptosis nor the execution of the apoptosis programme. In the first part, we present the most important proteins involved in apoptosis, from effectors to initiators. We present then the intracellular messages and the ‘intrinsic’ pathway that drive cells to death after they have undergone diverse types of stress and the extracellular signals that activate the ‘extrinsic’ pathway and drive cells to death on command. Various oncogenic alterations in apoptosis pathways have been identified, which lead to the identification of pharmacological targets.