Eukaryote differentiation

Complex multicellular eukaryotes differentiate irreversibly so that different cell types express a different profile of genes. Genes that are expressed are usually associated with swollen chromatin. Proteins found in active regions of the genome show characteristic modifications. 

Johnstone AP, Williams GT (1982) Role of DNA breaks and ADP-ribosyl transferase activity in eukaryotic differentiation demonstrated in human lymphocytes. Nature (London) 300 368-370... 

From work on chick embryo muscle cells the transient appearance of single-strand breaks in DNA, regulated by nuclear ADP-ribosyltransferase (ADPRT), has been proposed as part of a general mechanism for eukaryotic differentiation [1,2]. Investigation of the stimulation of quiescent lymphocytes has provided concordant results supporting this hypothesis, and has allowed a preliminary dissection of the molecular events of lymphocyte activation underlying immune responses. 

Tubulins arose very early during the course of evolution of unicellular eukaryotes and provide the machinery for the equipartitioning of chromosomes in mitosis, cell locomotion, and the maintenance of cell shape. The primordial genes that coded for tubulins likely were few in number. As metazoan evolution progressed, natural selection processes conserved multiple and mutant tubulin genes in response to the requirements for differentiated cell types (Sullivan, 1988). 

One peptide toxin from the mushroom Amanita phalhides, a-amanitin, is a specific differential inhibitor of the eukaryotic nuclear DNA-dependent RNA polymerases and as such has proved to be a powerful research tool (Table 37-2). a-Amanitin blocks the translocation of RNA polymerase during transcription. 

This subdivision is not based on the more usual macroscopic criteria it was made possible when techniques of subcellular biology became sufficiently refined for many more fundamental differences to become apparent. Some of the criteria differentiating eukaryotes and prokaryotes are given in Table 1.1. 

Single internal cytoplasm Periplasm as second compartment As for prokaryote plus internal vesicles and organelles As for unicellular eukaryote plus cell/cell differentiation Organs and extracellular body space Animals with a nervous system senses and a brain able to search external space... 

The approach recruited to chemical proteomics in Reference [17] is called SILAC (stable isotope labeling with amino acids in cell culture) and is important in comparative proteomics (Figure 1). SILAC works well with cultured mammalian cells, but prokaryotes defeat it by metabolizing the label (usually supplied in lysine and arginine) into other amino acids. For applications beyond cultured eukaryotic cells, the reductive methylation route to differential labeling [18] is among the alternatives [15]-... 

The differentiation, growth and division of eukaryotic cells is modulated by various influences, of which growth factors are amongst the most important for many cell types. A wide range of polypeptide growth factors have been identified (Table 10.1) and more, undoubtedly, remain to be characterized. Factors that inhibit cell growth also exist. For example, interferons and TNF inhibit proliferation of various cell types. 

Proteins of the cytoskeleton play a central role in the creation and maintenance of cell shapes in all tissues. They serve multiple roles in eukaryotic cells. First, they provide structural organization for the cell interior, helping to establish metabolic compartments. Second, cytoskeletal structures serve as tracks for intracellular transport, which creates and maintains differentiated cellular functions. Finally, the cytoskeleton comprises the core framework of cellular morphologies. 

Bestatin (ubenimex) is a potent inhibitor of aminopeptidase N and aminopeptidase B,89 which was isolated from a culture filtrate of Streptomyces olivoreticuli during the search for specific inhibitors of enzymes present on the membrane of eukaryotic cells.90 Inhibitors of aminopeptidase activity are associated with macrophage activation and differentiation, Bestatin has shown significant therapeutic effects in several clinical trials.91 In a multi-institutional study,92 patients with acute non-lymphocytic leukemia (ANLL) were randomized to receive either Bestatin or placebo orally after completion of induction and consolidation therapy, and concomitant with maintenance chemotherapy. Remission duration was prolonged in the Bestatin group, although this difference did... 

Liang P, Averboukh L, Pardee AB. 1993. Distribution and cloning of eukaryotic mRNAs by means of differential display refinements and optimization. Nucleic Acids Res... 

Liang P, Pardee AB. 1992. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. 

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