Expression posttranslational events

Thus, the differential expression of genes is required for the production of different proteins because each protein controls a distinct function. The function of many proteins is listed in Table 1.1. In addition, the protein profile of a cell can vary depending on the different kinds of modification of the same protein such modifications of protein may involve acetylation, phosphorylation, glycosylation, or association with lipid or carbohydrate molecules. These modifications in proteins occur as posttranslational events and alter the function of proteins. One example is the mitosis activator protein (MAP) kinase protein controlling the mitosis this protein is activated by phosphorylation to give MAP Kinase (MAPK), MAP kinase kinase (MAPKK), and MAP kinase kinase kinase (MAPKKK). The role of protein modification in the control of cellular activity is discussed later in this book. 

The human HS cycle can be considered broadly as a period which leads to the dramatic shift in activities of the transcriptional and translational machinery followed by eventual recovery and resumption of original activities preceding stress. Figure 1 depicts many of the key events in the HS cycle for a typical human cell line such as cervical carcinoma-derived HeLa cells. Most cells respond in an identical fashion, but some cell types that have distinctive HS responses. These differences are manifested by shifts in the relative concentrations of accumulated HS proteins and possibly in the pattern of posttranslational modifications. In all cases, however, the cellular stress response is heralded by induction of a specific transcription factor whose DNA binding activity facilitates increased expression of one or more of the stress-inducible genes. 

Prenylated proteins have characteristic C-terminal sequences. For example, the three allelic Ras proteins (H-Ras, K-Ras, and N-Ras) expressed in mammalian tissues contain a C-terminal tetrapeptide which begins with cysteine, and ends with either methionine or serine. This part of the molecule is referred to as the CaaX box where C = cysteine, a = an aliphatic amino acid, and X = a prenylation specificity residue. The first step in the posttranslational processing of Ras proteins utilizes FTase and farnesyl diphosphate (FPP) to covalently attach a farnesyl group to the cysteine thiol of the CaaX box. While subsequent processing events involve proteolytic removal of the aaX tripeptide and methylation of the resulting C-termi-nal carboxylate group, only the farnesyl modification is required for mutant Ras proteins to associate with the cell membrane and transform a cell.2-6... 

NAD is used in posttranslational modification of a variety of proteins, notably some of the proteins of the chromosomes. The chromosomes are composed of DNA, histones, and nonhistone proteins. The histones, which are distinguished by their high content of basic amino acids, serve as a scaffold and maintain the coiled and folded structiue of the DNA. The other proteins are used in regulating the expression of specific genes. Poly(ADP-ribose) polymerase catalyzes the attachment of ADP-ribose to various chromosomal proteins. This modification, shown in Figure 9.65A, is more dramatic than a simple methylation or phosphorylation. The enzyme uses NAD as a substrate. Here, NAD does not serve its usual role as an oxidant or reductant. The ADP-ribosyl moiety of NAD is donated to the acceptor protein. A molecule of nicotinamide is discharged with each event of... 

Studies of proteins present in a cell revealed a rich repertoire of expressed proteins way beyond what is expected from direct translation of the messages produced by a genome. Proteins can be modified posttranslationally by covalent attachment of one or more of several classes of molecules, by the formation of intramolecular or intermolecular linkages, by proteolytic processing of the newly synthesized polypeptide chain, or by any combination of these events. These modifications endow a protein with various properties that may be specifically required under a particular condition. 

The step labeled p in Figure 1 represents modification of primary proteins to render them functional examples would be posttranslational covalent modifications (e.g., phosphorylation) and binding with other proteins or other molecules. Represented within the set of steps p are the many regulatory events (other than transcription and translation) affecting gene expression and the overall physiology of the cell. 

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