Many carbohydrates besides Glucose (or D-Glucose) meet their catabolic fate in Glycolysis, after being transformed into one of the Glycolytic intermediates. The most significant are the storage polysaccharides Glycogen and Starch; the disaccharides Maltose, Lactose, Trehalose and Sucrose; and the monosaccharides Fructose (or D-Fructose), Mannose (or D-Mannose) and Galactose (or D-Galactose) (Ref.1). Glycogen in animal tissues and in microorganisms; and Starch in plants, are mobilized for use within the same cell by a phosphorolytic reaction catalyzed by Phosphorylase (that is Glycogen Phosphorylase in animals and in microorganisms or Starch Phosphorylase in plants). These enzymes catalyze an attack by Pi (Inorganic Phosphate) on the (Alpha1-4) glycosidic linkage[..]

In most organisms, the conversion of Galactose to the more metabolically useful Glucose-1-Phosphate is accomplished by the action of four enzymes that constitute the Leloir pathway. In the first step of this pathway, Beta-D-Galactose is epimerized to Alpha-D-Galactose by GALM (Galactose Mutarotase/Aldose 1-Epimerase) (Ref.1). The active site of GALM is positioned in a rather open cleft with the hydroxyl groups of Galactose lying within hydrogen bonding distance to a number of side chains, the reaction catalyzed by human GALM proceeds via Glu-307 (Glutamic acid-307) and His-176 (Histidine-176). Till now no diseases have been attributed to mutations in human GALM. The next step involves the ATP-dependent phosphorylation of Alpha-D-Galactose by GalK (Galactokinase) to[..]

CD40, a TNFR (Tumor Necrosis Factor Receptor) family member, conveys signals regulating diverse cellular responses, ranging from proliferation and differentiation to growth suppression and cell death. First identified and functionally characterized on B-Cells, CD40 is expressed on a plethora of different cell types, including B-Cells, macrophages, dendritic cells, endothelial cells, and fibroblasts, and this widespread expression accounts for the central role of CD40 in the regulation of immune response and host defense (Ref.1). Binding of CD40 with its counter receptor, CD154 (also termed CD40L [CD40 ligand] or GP39), acts on Antigen presenting cells and T-Cells in a bi-directional fashion, mediating both humoral and cellular immune responses (Ref.2). Unique to[..]

Eukaryotic transcription is a highly regulated process, and acetylation plays a major role in this regulation. Acetylation can occur on histones, DNA-binding TF (Transcription Factors), acetylases, nuclear import factors, non-nuclear proteins (Alpha-tubulin) and proteins that shuttle from the nucleus to the cytoplasm, such as the Importin-Alpha family of nuclear import factors. Acetylation can modify the recognition of DNA, the stability of proteins and the interaction between proteins. They regulate different cellular processes, such as microtubule function or nuclear import (Ref.1). By modifying chromatin proteins and transcription-related factors, these acetylases regulate diverse functions, including DNA recognition, protein-protein interaction, protein stability,[..]

In numerous processes that are vital for the development and maintenance of organism function, cells must communicate crucial information to respond appropriately to the changing environment. As such, RTKs (Receptor Tyrosine Kinases) are transmembrane proteins, which, on receiving an external stimulus, respond by transmitting a signal to the inside of the cell. Of all the RTKs that are found in the human genome, the Eph Receptor family and their ligands the Ephrins, constitutes the largest family.The Eph family of RTKs which has 14 members and their ligands, the Ephrins, are prominently involved in several developmental processes such as boundary formation, cell migration, axon guidance, synapse formation and angiogenesis. In vertebrates, Eph Receptors are divided into[..]

The DNA damage response network involves several kinases to inactivate CDK/ cyclin complexes and result in cell cycle arrest for DNA repair. In the presence of DNA damage or incomplete DNA replication, eukaryotic cells activate cell cycle checkpoints that temporarily halt the cell cycle to permit DNA repair or completion of DNA replication to take place. In the presence of extensive damage or absence of timely repair, these checkpoint-signaling pathways may also trigger a pathway that effects programmed cell death or apoptosis. DNA damage-activated cell cycle checkpoints are regulated in part by the phosphoinositide kinase family of checkpoint components, including the yeast Rad3 in Schizosaccharomyces pombe, Mec1/Tel1 in Saccharomyces cerevisiae, mammalian ATM (Ataxia[..]

Inositol lipid-specific PLC (Phospholipase-C) isozymes are key signaling proteins in the cellular action of many hormones, neurotransmitters, growth factors, and other extracellular stimuli. PLC are soluble proteins that are partly cytosolic and partly associated with membrane. The PLC family in human is comprised of 13 subtypes. On the basis of their structure, they have been divided into six classes, PLC-Beta (Beta 1, 2, 3 and 4), PLC-Gamma (Gamma 1 and 2), PLC-Delta (Delta 1, 3 and 4), PLC-Epsilon, PLC-Zeta and PLC-Eta (Eta1 and 2) types. The molecular weights of each are 85kDa for the Delta form, 120-155kDa for both the Beta and Gamma forms, and 230-260kDa for the Epsilon form. These groups also differ in the mechanisms by which the isozymes are activated in[..]

The condensation of DNA into an ordered chromatin structure allows the cell to solve the topological problems associated with storing huge molecules of chromosomal DNA within the nucleus. DNA is packaged into chromatin in orderly repeating protein-DNA complexes called nucleosomes. Each nucleosome consists of approximately 146bp of dsDNA (double-stranded DNA) wound 1.8 times around a histone octamer.Two molecules each of H2A, H2B, H3, and H4 comprise the histone ramp around which the DNA superhelix winds. Stretches of DNA upto 100bp separate adjacent nucleosomes. Multiple nuclear proteins bind to this linker region, some of which may be responsible for the ordered wrapping of strings of nucleosomes into higher-order chromatin structures (Ref.1).Chromatin assembly[..]

Nucleotide excision repair (NER) is the main pathway used by mammals to remove bulky DNA lesions such as those formed by UV light, environmental mutagens, and some cancer chemotherapeutic adducts from DNA. Deficiencies in NER are associated with the extremely skin cancer-prone inherited disorder xeroderma pigmentosum. Although the core NER reaction and the factors that execute it have been known for some years, recent studies have led to a much more detailed understanding of the NER mechanism, how NER operates in the context of chromatin, and how it is connected to other cellular processes such as DNA damage signaling and transcription(Ref.1). The NER process requires the action of more than 30 proteins in a stepwise manner that includes damage recognition, local[..]

The optimum functioning of the immune system is crucial for human survival. The invading pathogens are encountered by the cells of the immune system, which include T-Cells, B-Cells, macrophages, neutrophils, basophils, eosinophils, endothelial cells, or mast cells. These cells have distinct roles in the immune system, and cell-to-cell communication among these cells is an indispensable prerequisite for the stimulation of the optimum immune response. In the process, cytokines serve as signal molecules for communication that are induced by several cell-signaling cascades. NFATs (Nuclear factors of activated T-Cells), a family of transcription factors expressed by diverse cell types of the immune system plays a pivotal role in the process. Originally described in[..]

4-1BB is an inducible T cell surface receptor belonging to the tumor necrosis factor receptor super family. It presents on the surfaces of activated CD4+ and CD8+ T cells, monocytes and B lymphocytes. 4-1BB signaling is activated by binding to its high-affinity ligand 4-1BBL which is expressed on the surface of antigen-presenting cell. 4-1BB signaling promotes cell growth, T cell differentiation and survival of immune cells (Ref.1&2).4-1BB mediates its action via association with TRAF1, TRAF2 and TRAF3. 4-1BB binding to TRAF2 and TRAF3/ cIAP complex leads to activation of the NIK. NIK activates NF-kB via the IKK-alpha/ NFKBIA pathway (Ref.2, 3, 4&5).NF-kB induces transcription of Bcl-XL, Bcl-2 and BFL1, and thus promotes survival of immune cells (Ref.6,[..]

Rho is a member of the Ras superfamily of small GTP-binding proteins that play a central role in diverse biological processes such as Actin cytoskeleton organization, Microtubule dynamics, Gene transcription, Oncogenic transformation, Cell cycle progression, Adhesion and Epithelial wound repair. To date, 20 genes encoding different members of the Rho family have been identified in the human genome, and each one acts as a molecular switch to control distinct biochemical pathways. The mammalian Rho GTPase family currently consists of three subfamilies, Rho (RhoA, RhoB and RhoC), Rac (Rac1, Rac2 and Rac3) and CDC42 (Cell Division Cycle-42) (CDC42Hs and G25K). Rho proteins cycle between an active GTP-bound state and an inactive GDP-bound state. Their activation state is[..]