Caspase Regulation

Molecular mechanisms of caspase regulation during apoptosis. Nature Reviews Molecular Cell Biology, 5, 897-907. 

Unprogrammed activation of the caspases has serious consequences for the cell. Therefore, activation of caspases is strictly controlled. In the normal state of the cell, the caspases are maintained in an inactive state but can be rapidly and extensively activated by a small inducing signal. Control of caspase activity occurs at two levels. The first level of caspase regulation involves the conversion of the caspase precursors, the zymogens, to the active forms in response to inflammatory or apoptotic stimuli. The second level of caspase control involves the specific inhibition by binding of natural inhibitors. 

Apoptotic executioner caspases (caspase-3, -6, -7) constitute a subgroup of the caspase family. These proteases are the workhorses of the apoptotic process as they are responsible for cleaving many down-stream substrates important for cellular morphology, organelle homeostasis, cell cycle arrest, and regulation of transcription and translation. 

Festjens N, Comelis S, Lamkanfi M et al (2006) Caspase-containing complexes in the regulation of cell death and inflammation. Biol Chem 387 1005-1016... 

Also, phosphorylation of Akt results in activation of sterol regulatory-element binding protein 1 (SREBP1), a key transcription factor involved in regulation of lipogenic enzymes. In addition, some of the effects of insulin on cell proliferation and survival may be explained by an Akt-dependent inhibition of apoptosis through phosphorylation and inactivation of proa-poptotic proteins (e.g., BAD, Caspase 9). 

CD C14 C14.001 Caspase-1 Potential drug target for down-regulation of the inflammatory mediator, interleukin 1beta, which could ameliorate inflammation and endotoxic shock... 

Bacellar H, Munoz A et al (1994) Temporal trends in the incidence of HIV-l-related neurologic diseases Multicenter AIDS Cohort Study, 1985-1992. Neurology 44(10) 1892-1900 Banki K, Hutter E et al (1998) Molecular ordering in HIV-induced apoptosis. Oxidative stress, activation of caspases, and cell survival are regulated by transaldolase. . J Biol Chem 273(19) 11944-11953... 

Tun C, Guo W, Nguyen H, Yun B, Libby RT, Morrison RS, Garden GA (2007) Activation of the extrinsic caspase pathway in cultured cortical neurons requires p53-mediated down-regulation of the X-linked inhibitor of apoptosis protein to induce apoptosis. J Neurochem 102 1206-1219... 

RASSi c M, LIEBERHERR M, CHAUMAZ G, POINTILLART A and COURNOT G (2002) Down-regulation of osteoclast diferrentiation by daidzein via caspase 3. JBone Min Res 17, 630-38. 

Wang SL, Hawkins CJ, Yoo SJ, Muller HA, Hay BA 1999 The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. Cell 98 453-463... 

Regulation of programmed cell death (apoptosis) is not only important in normal cell development and homeostasis [1, 2], but also during the process of carcinogenesis [3], Apoptosis is suppressed in most cancer cells and induction of apoptosis is one cancer treatment strategy [4], There are many processes and factors that can be modulated to induce cancer cell apoptosis, such as regulation of factors involved in cell cycle arrest [5], protein kinase modulation [6], caspase family activation [7], and the balance in expression between Bcl-2 family members [8],... 

---