US EPA

7438154 

Journal Article 

Death Receptors 

Shankar, S; Srivastava, RK; , 

2007 

Humana Press 

Totowa, NJ 

Apoptosis, Cell Signaling, and Human Diseases 

219-261 

10.1007/978-1-59745-199-4_11 

http://link.springer.com/10.1007/978-1-59745-199-4_11
Exit
 

Apoptosis is a genetically controlled process that plays important roles in embryogenesis, metamorphosis, cellular homeostasis, and as a defensive mechanism to remove infected, damaged or mutated cells. Although a number of stimuli trigger apoptosis, it is mainly mediated through at least three major pathways that are regulated by (1) the death receptors, (2) the mitochondria, and (3) the ER (endoplasmic reticulum). Under certain conditions, these pathways may crosstalk to enhance apoptosis. Death receptor pathways are involved in immune-mediated neutralization of activated or autoreactive lymphocytes, virus-infected cells, and tumor cells. Consequently, dysregulation of death receptor pathway has been implicated in the development of autoimmune diseases, immunodeficiency, and cancer. Increasing evidence indicates that mitochondrial and ER pathways of apoptosis play a critical role in cytokine receptor-mediated apoptosis. Considerable evidence has accrued about the effects of dysregulation of these pathways on drug resistance. Recent data indicate that BH3-only proteins act as mediators that link various upstream signals, including death receptors and DNA damage signaling, to the mitochondrial and the ER pathway. Evidence suggests that these proteins may function as integrators of damage signals, and may be the final decision point as to whether a cell lives or dies. This chapter discusses the molecular mechanisms of apoptotic pathways regulated by the death receptors, mitochondria and endoplasmic reticulum and their potential applications to cancer therapy.