Posttranslational control

Several models, yet relatively little direct evidence has been presented to explain the genetic regulation of interferon production. No matter what model may be built to accomodate all known facts, it should be composed, in its simplest form, of an operon (interferon gene), a repressor protein, and a mRNA. The repressor protein may combine with the operator of the operon (referred to as transcriptional control in Fig. 7) in this state, the interferon gene would be repressed. It would be derepressed if the repressor is inactivated, e.g. following contact of the cell with the interferon inducer. The derepressed interferon gene would then be transcribed to mRNA, which in turn is translated to interferon. Hypothetically, the repressor protein may also combine with the mRNA for interferon (referred to as translational control), and even with the interferon molecule itself (referred to as posttranslational control in Fig. 7). 

S-acylated proteins include many GTP-binding regulatory proteins (G proteins), including most a subunits of heterotrimeric G-proteins and also many members of the Ras superfamily of monomeric G proteins, a number of G protein-coupled receptors, several nonreceptor tyrosine kinases, and a number of other signaling molecules, -acylation is posttranslational and reversible, a property that allows the cell to control... 

Phosphorylation is the reversible process of introducing a phosphate group onto a protein. Phosphorylation occurs on the hydroxyamino acids serine and threonine or on tyrosine residues targeted by Ser/Thr kinases and tyrosine kinases respectively. Dephosphorylation is catalyzed by phosphatases. Phosphorylation is a key mechanism for rapid posttranslational modulation of protein function. It is widely exploited in cellular processes to control various aspects of cell signaling, cell proliferation, cell differentiation, cell survival, cell metabolism, cell motility, and gene transcription. 

Protein tyrosine kinases (PTKs) are enzymes (EC 2.7.1.112) that catalyze the transfer of the y-phosphate group of ATP to tyrosine residues of protein substrates. The activity of PTKs is controlled in a complex manner by posttranslational modifications and by inter- and intramolecular complex formations. 

Methylation plays an important role in transcriptional regulation and a lesser role in signal transduction. " Histones are heavily methylated proteins. Single, double, or triple methylated lysines play an important role on histones. Lysine methylation is a more subtle transcriptional control than acetylation. Lysine methylation has come to light in another protein known as p53. p53 is a protein expressed in low levels in the cell and stabilized by posttranslational modifications including phosphorylation, acetylation, and now N-methylation. There are several C-terminal lysines on p53 that increase its stability. The addition of the methylation modifications adds complexity to p5 3 and fine-tunes its activity and ultimately suppresses tumor formation. ... 

Ubiquitin ligases largely control the substrate specificity of ubiquitin-conjugation reaction. The temporal specificity of ubiquitin conjugation to substrates by these enzymes is provided by regulation of the ligase activity. Activity of ubiquitin ligases can be modulated by posttranslational modification such as phosphorylation and by allosteric modification of the enzyme, or by attachment to UbL proteins. 

Ca by molecules critical to synaptic plasticity has been well documented. Temporal specificity of ubiquitination can also be achieved by controlling the vulnerability of the substrate to ubiquitination by posttranslational modification such as phosphorylation. Phosphorylation makes jun and C/EBP resistant to ubiquitin-proteasome-mediated degradation. ... 

Wickner, S., M. R. Maurizi, and S. Gottesman. Posttranslational quality control folding, refolding, and degrading proteins. Science. 286 1888-1893.1999. 

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