Posttranslational function

The Golgi apparatus is a stack of flattened vesicles that functions in posttranslational processing and sorting... 

The transcriptional activity of NRs is also modulated by various posttranslational modifications of the receptors themselves or of their coregulatory proteins. Phosphorylation, as well as several other types of modification, such as acetylation, SUMOylation, ubiquitinylation, and methylation, has been reported to modulate the functions of NRs, potentially constituting an important cellular integration mechanism. In addition to the modifications of the receptors themselves, such modifications have been reported for their coactivators and corepressors. Therefore, these different modes of regulation reveal an unexpected complexity of the dynamics of NR-mediated transcription. 

There has been an extensive search for additional opioid receptor genes with homology to p, 8, and k receptors which was, however, unsuccessfiil. It is likely, therefore, that the functional properties of the subdivision of p, 8, and k receptors as well as that of the e and X receptors results from alternate mRNA processing, posttranslational modification of the receptor, and/ or from the formation of homo- and heterodimeric receptor complexes. 

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. 

In the x-ray structure of rhodopsin, an amphipathic helix runs parallel to the membrane from the intracellular end of TM-VII beneath the seven-helical bundle to the other side of TM-I and TM-II. At this point, one or more Cys residues are often found and are known to be subject to a dynamic posttranslational modification with palmitic acid residues. Like the phosphorylation event, the palmitoylation process appears to be dynamically regulated by receptor occupancy and is also involved in the desensitization phenomenon. The two posttranslational modifications can influence each other. For example, the conformational constraint induced by palmitoylation may alter the accessibility of certain phosphorylation sites. Like the phosphorylation process, the functional consequences of palmitoylation also appear to vary from receptor to receptor. 

Figure 1 Covalent modifications of DNA and histones play a fundamental role in the regulation of differentiation and development. The writers, readers, and erasers of this dynamic code are potentially amenable to modulation with small molecules. Lysine methylation is a critical posttranslational modification influencing chromatin function (PMT = protein lysine methyltransferase, royal family proteins bind KMe, KDM = lysine demethylase).

General Membrane Function Membrane Composition Phospholipid Bilayer Membrane Structure Posttranslational Modification Membrane Fluidity Diffusion in Membranes... 

Although FTase inhibitors influence the farnesylation of Ras they are likely to interfere with the posttranslational modifications of other CAAX-containing proteins as well. Apart from the approximately 20 farnesylated proteins that are known today, farnesylation is also required for normal Ras function which in turn is critical for normal cell viability. For these reasons farnesyltransferase... 

There is now a growing interest in proteomic studies of brain synapses. Recent studies have revealed a high molecular complexity in the pre- and postsynaptic areas, with thousands of proteins [6]. An important investigation for the future is to identify posttranslational modifications, miscoded as well as misfolded proteins, likely to have an impact on different aspects of synaptic function as a response to the environment as well as to the lifestyle. The first challenge is to identify and quantify the presence and variation of different proteins in key structures of the pre- and postsynaptic areas in order to relate protein structures to synaptic function. Recently, a new model has been presented describing the molecular complexity of the synapse with important aspects in emotions, thinking, memory, and consciousness [7] (Fig. 17.2). 

Cell cycle progression, apoptosis, DNA damage and DNA repair are cellular functions that are regulated by several mechanisms. One such important regulatory mechanism is posttranslational modification of histone and non-histone proteins. Myriad of reports have been shown that acetylation of non-histone proteins apart from histones, contributes in major to these processes. 

Figure 3. Role of nonhistone protein acetylation in maintaining cellular homeostasis- mis-regulation and disease connection (a) Acetylation of nonhistone proteins are associated with active or repressed chromatin architecture as guided by suitable cellular signals for maintenance of gene expression. Misreg-ulation of HAT function leads to diseased state, where chromatin architecture is altered than under normal condition. In a parallel way the posttranslational modification status of these proteins may act as versatile tool to diagnose the various stages of disease manifestation e.g. probable involvement of acetylated NPMl modulating its stress response function can lead us to use it as a marker for various disease states, (b) Acetylation of nonhistone proteins in connection to diseases like Cancer, AIDS, Diabetes and others. (See Colour Plate 14.)...

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