Role in cellular differentiation

The synthesis of secondary amines from azides is efficient in terms of chemos-electivity [57] and has found valuable applications in the preparation of diamines [58,59], m-alkylaminoboronic esters [60], and in Diels-Alder-based amination reactions [61]. A convenient general route to open-chain polyamines, which play major roles in cellular differentiation and proliferation, has also been developed using the reductive alkylation of aliphatic aminoazides by (co-halogenoalk-yi)dichloroboranes as a key step [62] (Scheme 21). 

Greenfield, S. (1996). Non-classical actions of cholinesterases role in cellular differentiation, tumorigenesis and Alzheimer s disease. Neurochem. Int. 28 485-90. 

Jetten, A. M. and Joo, J. H. (2006) Retinoid-related orphan receptors (RORs) roles in cellular differentiation and development. Adv. Dev. Biol. 16, 314-354. 

At present the events triggering and the mechanism controlling muscle differentiation are not well understood they may include changes in chromatin structure, gene amplification, and specific DNA and/or protein modification. One such modification, namely, poly(ADP-ribosyl)ation of nuclear proteins has recently attracted much attention and several studies have indicated that the enzyme poly(ADP-ribose) synthetase plays a role in cellular differentiation [6-9]. This enz)mie is a nuclear chromatin-associated protein which catalyzes covalent modification of both histone and nonhistone protein acceptors (for reviews see [10-13]). The synthetase is activated by DNA strand breaks and it has been suggested that DNA fragmentation and the consequent increase in poly(ADP-ribose) activity are obligatory events for chick muscle differentiation [6]. 

The spatial and steric requirements for high affinity binding to protein kinase C (PKC), a macromolecule that has not yet been crystallized, were determined. Protein kinase C plays a critical role in cellular signal transduction and is in part responsible for cell differentiation. PKC was identified as the macromolecular target for the potent tumor-promoting phorbol esters (25). The natural agonists for PKC are diacylglycerols (DAG) (26). The arrows denote possible sites of interaction. 

While activation of HSFl and HSF2 results in the increased expression of HS genes, recent studies indicate that there are distinct differences between these transcription factors. As noted previously, HSFl is the heat-inducible form of the HS factors, whereas HSF2 is activated by hemin (Sistonen et al., 1992). This observation has indicated a possible role of HSF2 in cellular differentiation. It also indicates that the activation domains of the two transcription factors are quite different. Presumably the DNA binding properties of the two transcription factors are similar, but recent experiments indicate otherwise (Kroger and Morimoto,... 

Epithelial cells are interconnected at the apical (mucosal) side by a complex network of proteins, called the tight junctions (TJ). First thought to have merely a static role in restricting access of compounds present in the luminal fluid to the underlying subepithelial tissue and systemic circulation by the paracellular pathway, TJ are known today to be dynamic structures involved in cellular differentiation, cell signaling (Harder and Margolis 2008), polarized vesicle trafficking, and protein synthesis. 

Several isoforms of tyrosine protein kinase play roles in cellular growth and differentiation. The assay of Boutin et al. (1992), exploits the use of hydrophilic interaction chromatography to separate hydrophilic peptides. 

GSK-3 is highly conserved between different eukaryotic species, displaying close DNA sequence homology. Similarly, high amino acid sequence homology indicates that GSK-3 has conserved structure and fimction in different species. GSK-3 exists in two isoforms encoded by different genes in mammals, GSK-3a and GSK-3P [1]. Both isoforms display a ubiquitous tissue expression pattern [2], but although structurally similar, they are not fimctionally redim-dant. The differential expression of GSK-3a and GSK-3P indicates that they may display different roles in cellular functions and tissues. 

Retinoids play a key role in cellular development, differentiation and growth. They have been shown to affect cell cycle progression and apoptosis in a variety of cell lines, although the exact mechanisms are not clearly defined. The effects of retinoids on a number of molecules involved in intracellular signaling have been investigated in an ongoing attempt to delineate possible pathways. 

The recent demonstration that l,25-(OH)2D stimulates the differentiation of myeloid leukemia cells (MI and human HL-60 cells) into monocytes in a dose-dependent manner, 02,103suggests a potential role for vitamin D metabolites in cellular differentiation. Somewhat higher doses of l,25-(OH)2D2 are required than those effective in cultures of embryonic bone or chick embryonic Intestine, but the compounds that show maximum effectiveness in terms of calcium action also show maximum effect in stimulating the differentiation process. 

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