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Mechanisms of Programmed Cell Death through Biophysics and Structural Biology

Yigong Shi Department of Molecular Biology;Princeton University;Princeton;NJ 08544;USA

  Apoptosis, or programmed cell death, is central to the development and homeostasis of metazoans. Dysregulation of apoptosis leads to a variety of human pathologies, including cancer, autoimmune diseases, and neurodegenerative disorders. Since the concept of apoptosis was established in 1972, research efforts have led to the identification of hundreds of genes that govern the initiation, execution, and regulation of apoptosis primarily in three model species: C. elegans, Drosophila, and mammals. The central pathway of apoptosis is conserved among the three species. The executioners of apoptosis in all species are the caspases, cysteine proteases with a substrate specificity for aspartate. The control of apoptosis is dictated by the regulation of caspase activation, inhibition, and removal of inhibition. Over the past decade, many key events in caspase regulation have been documented at the molecular and cellular level. An earlier focus on the genetic and cell-biological characterization has now been complemented by biochemical, biophysical, and structural biological investigation, giving rise to an unprecedented level of clarity in……