Intracellular Regulation

The abihty of the cofactors to activate caspases is regulated by a number of other proteins that appear to interact directly with the cofactors. 

These proteins interact with the cofactor FADD in death-receptor-mediated apoptosis (see 15.4) and block its activating effect. 

The antiapoptotic Bcl-2 family members control apoptosis by various mechanisms without directly binding to the caspases. Bcl-2 proteins can interact with cofactors and inhibit their activity. They can also act antiapoptotically by binding to mitochondria and interfering with release of cytochrome c. Furthermore, they can interact with other proapoptotic proteins, e.g. with propapoptotic members of their own family. 

These proteins inhibit apoptosis but their site of action is imcertain. Some of them apparently bind to caspases and inhibit these directly. 

4 Stress-mediated Apoptosis the Cytochrome c/Apafl Pathway 

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Lohka MJ, Hayes MK, Mailer JL 1988 Purification of maturation-promoting factor, an intracellular regulator of early mitotic events. Proc Natl Acad Sci USA 85 3009—3013 Mailer JL, Butcher FR, Krebs EG 1979 Early effects of progesterone on levels of cyclic adenosine 3 5 -monophosphate in Xenopus oocytes. J Biol Chem 254 579-582 Masui Y 1967 Relative roles of the pituitary, follicle cells, and progesterone in the induction of oocyte maturation in Ranapipiens. J Exp Zool 166 365-375 Masui Y, Markert CL 1971 Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. J Exp Zool 177 129-145... 

It is uncertain whether the intrinsic timer in OPCs primarily controls the onset of differentiation, the cessation of proliferation, or both. It seems likely, however, that the timer at some point interacts with the cell-cycle control system that regulates progress through the cell cycle. As the cells stop dividing and differentiate in Gl, it is the part of the control system that operates in G1 that is most likely to be relevant. In principle, the components of the cell-cycle control system could be components of the timer. The timer, for example, could depend on a decrease in one or more positive intracellular regulators, such as a cyclin or a Cdk... 

Lindmark, T., Y. Kimura, and P. Artursson. Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty adds in Caco-2 cells, J. Pharmacol. Exp. Ther. 1998, 284, 362-369... 

Neuronal phosphoproteins differ considerably in the number and types of amino acid residues phospho-rylated. The complexity of intracellular regulation is underscored by the now numerous and well-established observations of numerous proteins that are phosphory-lated on more than one amino acid residue by more than... 

Moonga BS, Moss DW, Patchell A, Zaidi M. 1990. Intracellular regulation of enzyme secretion from rat osteoclasts and evidence for a functional role in bone resorption. J Physiol 429 29-45. 

Signal transducers and intracellular regulators Caspases Serin proteases Bcl-2 family... 

Intermittent plasma growth hormone triggers tyrosine phosphorylation and nuclear translocation of a liver-expressed, Stat 5-related DNA binding protein. Proposed role as an intracellular regulator of male-specific liver gene transcription. J. Biol. Chem. 270, 13262-13270. 

Extra- and Intracellular Regulators of Prostaglandin Secretion by Mammalian Reproductive Tissues Alexander V. Sirotkin, Hyuk B. Kwon, Alexander V. Makarevich, Mark R. Corkins, Jan Kotwica, Pierre-Guy Marnet, Jozef Bulla, and Ladislav Hetdnyi... 

Extra- and Intracellular Regulators of Prostaglandin Secretion by Mammalian Reproductive Tissues... 

Lohka, M. J., Hayes, M. K., and Mailer, J. L. (1988). Purification of maturation-promoting factor, an intracellular regulator of early mitotic events. Proc. Natl Acad. Scl U.S.A. 85, 3009-3013. 

Tachibana, R. et al, 1998. Intracellular regulation of macromolecules using pH-sensitive liposomes and nuclear localization signal qualitative and quantitative evaluation of intracellular trafficking. Biochemical and Biophysical Research Communications, 251, 538-544. 

Mariathasan S, Monack DM. Inflammasome adaptors and sensors intracellular regulators of infection and inflammation. Nature Rev Immunol 2007 7 31-40. 

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