apoptosis
• Discover and rediscovery along 2 century
• Final name, apoptosis: Currie and collegue 1972
• Different morphological
Feature of apoptotic cell
• Shrinkage in volume of the cell and its nucleus
• Loss of adhesion to neighboring cells
• Formation of blebs at the cell surface
• Chromatin fragmentation
• Engulfment by phagocytotic cell
apoptosis
• Important in maintaining homeostatis in multicellular organism
• Failure to regulate apoptosis can result serious damage to the organism
Apoptosis: a biochemistry view
• Caspase, the central executioner
• Degrade the protein and activate other protein
• Nuclease
• Degradation of cytoskeleton: lamina nukleus, fodrin, gelsolin
• Activate p21: bebling effect
Caspase activation
• Processing by an upstream caspase
• Induced proximity
• Association with a regulatory sub unit
Caspase targeting
• Protein kinase; FAK, PKB, PKC dan Raf1
• Lamins
• Protein of cytoskeleton; intermediate filament, actin, tubulin, gesolin
• Endonuclease: caspase activated DNase
Apoptosis as a protein-protein interaction
• Caspase prodomain have a protein-protein interaction module
• Bcl-2: control of cell death. Direct binding to CED-4, facilitate cythocrome c release from mt
Bcl-2 family members
• Intrinsic pathway apoptosis
• Pro-apoptotic: Bad, Bax
• Antiapoptotic: Bcl-xL, Bcl-W, and Bcl-2
Bcl-2 family members and Caspase activation
• Bcl-2 members form channel to facilitate protein transport
• Bcl-2 members interact with other protein to form a channel
• Bcl-2 members induce rupture of the outer mitochondrial membrane
Is caspase activation the defining feature of apoptotic cell death?
• Most if not all
• Activation apoptotic program without caspase
Daftar Pustaka dan Rujukan
1. Gerald Karp. “Cell And Molecular Biology: Concept and Experiments 6th edition.” Wiley
2. Michael O Hengartner. “ The Biochemistry of Apoptosis”. Nature Insight Review Article
3. http://www.nature.com/nature/insights/6805.html
Top Related