Caspases genes

Viability and Phenotype in Knockout Mice with Deletion of Caspase Genes... 

Pompl PN, Yemul S, Xiang Z, Ho L, Haroutimian V, Purohit D, Mohs R, Pasinetti GM (2003) Caspase gene expression in the brain as a function of the clinical progression of Alzheimer disease. Arch Neurol 60 369-376... 

Wang, Y. and X. Gu. Functional divergence in the caspase gene family and altered functional constraints statistical analysis and prediction. Genetics 158 1311-1320, 2001. 

The caspase gene family contains 14 mammalian members of these, 11 human enzymes have been identified (Table 1). This gene family is composed of two major subfamilies ICE (caspase-1 inflammation group) and ICH (ICE and Ced-3 homologue apoptosis group) [13]. All the caspases share similarities in their amino acid sequence, structure, and substrate specificity. They are expressed as proenzymes or zymogens... 

Figure 2. Mechanisms and signalings of neuronal death. Death can be initiated at the membrane by activation of death domain receptors (DDR), or by intracellular signalings through oxidative stress (and the production of reactive oxigen species, ROS), perturbed calcium homeostasis, mitochondrial dysfunction (release of cytochrome c, cytC), activation of caspases, as well as reactivation of cell cycle genes such as the transcription factor E2F (see text). Interconnections have been demonstrated (dotted lines) depending on the apoptotic context...

Figure 3. The many ways to lose a HAT. Decreased amounts of functional CBP protein and subsequent CBP s loss of function has been observed in different contexts of neurological disorders and neuronal apoptosis. RTS (Rubinstein-Taybi Syndrome) results from a mutation on one cbp gene allele. In several cases of polyQ diseases, CBP can be sequestred by the mutated polyQ proteins, forming aggregates in the cytoplasm or the nucleus. CBP proteasomal degradation was also shown to be favored by polyQ proteins. CBP is a caspase-6 substrate in cerebellar granule neurons (CGN) deprived of potassium modeling caspase-dependent apoptosis. Finally, cbp gene repression has been observed in oxidative stress-induced death of a motomeuronal cell line. The mechanisms by which CBP levels are reduced in motomeurons of ALS mice is still unknown...

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