Open Access
Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis
Reads0
Chats0
TLDR
Caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases as discussed by the authors, and they play critical roles in initiation and execution of this process.Abstract:
■ Abstract Apoptosis is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli. Studies performed over the past 10 years have demonstrated that proteases play critical roles in initiation and execution of this process. The caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases. Caspases are synthesized as relatively inactive zymogens that become activated by scaffold-mediated transactivation or by cleavage via upstream proteases in an intracellular cascade. Regulation of caspase activation and activity occurs at several different levels: ( a) Zymogen gene transcription is regulated; ( b) antiapoptotic members of the Bcl-2 family and other cellular polypeptides block proximity-induced activation of certain procaspases; and ( c) certain cellular inhibitor of apoptosis proteins (cIAPs) can bind to and inhibit active caspases. Once activated, caspases cleave a variety of intracellular polypeptides, including major structural elements of the cytoplasm and nucleus, components of the DNA repair machinery, and a number of protein kinases. Collectively, these scissions disrupt survival pathways and disassemble important architectural components of the cell, contributing to the stereotypic morphological and biochemical changes that characterize apoptotic cell death.read more
Citations
More filters
Journal ArticleDOI
The biochemistry of apoptosis
TL;DR: The basic components of the death machinery are reviewed, how they interact to regulate apoptosis in a coordinated manner is described, and the main pathways that are used to activate cell death are discussed.
Journal ArticleDOI
Molecular mechanisms of caspase regulation during apoptosis
Stefan J. Riedl,Yigong Shi +1 more
TL;DR: The present understanding of caspase regulation during apoptosis is described and biochemical and structural studies have led to important advances in understanding the underlying molecular mechanisms of cispase regulation.
Journal ArticleDOI
Mechanisms of Caspase Activation and Inhibition during Apoptosis
TL;DR: Current understanding of caspase regulation during apoptosis is presented and structural and biochemical studies on procaspases, IAPs, Smac/DIABLO, and apoptosome are reviewed.
Journal ArticleDOI
Signal transduction by tumor necrosis factor and its relatives
Véronique Baud,Michael Karin +1 more
TL;DR: This review focuses on proteins that transduce the signals generated at TNF receptors to nuclear targets such as AP-1 and NF-kappaB, which are likely to be used by other members of the TNF family.
Journal ArticleDOI
Comparative Genomics of the Eukaryotes
Gerald M. Rubin,Mark Yandell,Jennifer R. Wortman,George L. Gabor,Miklos,Catherine R. Nelson,Iswar K. Hariharan,Mark E. Fortini,Peter W. Li,Rolf Apweiler,Wolfgang Fleischmann,J. Michael Cherry,Steven Henikoff,Marian P. Skupski,Sima Misra,Michael Ashburner,Ewan Birney,Mark S. Boguski,Thomas Brody,Peter Brokstein,Susan E. Celniker,Stephen A. Chervitz,David Coates,Anibal Cravchik,Andrei Gabrielian,Richard F. Galle,William M. Gelbart,Reed A. George,Lawrence S.B. Goldstein,Fangcheng Gong,Ping Guan,Nomi L. Harris,Bruce A. Hay,Roger A. Hoskins,Jiayin Li,Zhenya Li,Richard O. Hynes,Steven J.M. Jones,Peter M. Kuehl,Bruno Lemaitre,J. Troy Littleton,Deborah K. Morrison,Christopher J. Mungall,Patrick H. O'Farrell,Oxana K. Pickeral,Chris Shue,Leslie B. Vosshall,Jiong Zhang,Qi Zhao,Xiangqun H. Zheng,Fei Zhong,Wenyan Zhong,Richard A. Gibbs,J. Craig Venter,Mark Raymond Adams,Suzanna E. Lewis +55 more
TL;DR: The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.
References
More filters
Journal ArticleDOI
Annexin-1 and Peptide Derivatives Are Released by Apoptotic Cells and Stimulate Phagocytosis of Apoptotic Neutrophils by Macrophages
Michael Scannell,Michelle B. Flanagan,Andreas deStefani,Andreas deStefani,Kieran Wynne,Gerard Cagney,Catherine Godson,Paola Maderna +7 more
TL;DR: It is ascertained that annexin-1 and peptide derivatives are putative prophagocytic factors released by apoptotic cells that promote phagocytosis of apoptotic PMN by M[phi] and differentiated THP-1 cells.
Journal ArticleDOI
Selective cleavage of nuclear autoantigens during CD95 (Fas/APO-1)-mediated T cell apoptosis.
TL;DR: It is demonstrated here that T cell apoptosis mediated by CD95 (Fas/APO-1) is associated with substantial cleavage of a subset of nuclear autoantigens, reinforcing the hypothesis that apoptosis is accompanied by selective cleaving of key substrates and not by a generalized degradation of intracellular material.
Journal ArticleDOI
Methamphetamine induces neuronal apoptosis via cross-talks between endoplasmic reticulum and mitochondria-dependent death cascades
TL;DR: Findings indicate that METH causes neuronal apoptosis in part via cross‐talks be¬tween ER‐ and mitochondria‐generated processes, which cause activation of both caspase‐dependent and ‐independent pathways.
Journal ArticleDOI
Actin cleavage by CPP-32/apopain during the development of apoptosis
Tetsuo Mashima,Mikihiko Naito,Kohji Noguchi,Douglas K. Miller,Donald W. Nicholson,Takashi Tsuruo,Takashi Tsuruo +6 more
TL;DR: The present results indicate that actin is the substrate of CPP-32/apopain(-like) protease both in vitro and in vivo and suggest the role of actin in the control of cell growth and apoptosis.
Journal ArticleDOI
Microfilament reorganization during apoptosis: the role of Gas2, a possible substrate for ICE-like proteases.
TL;DR: The evidence accumulated here could represent a first example of a mechanism linking apoptosis with the co‐ordinated microfilament‐dependent cell shape changes, as possibly mediated by an interleukin‐1 beta‐converting enzyme (ICE)‐like dependent proteolytic cleavage of the Gas2 protein.