Protein synthesis regulation in eukaryotes is important for the modulation of gene expression. The process of mRNA translation/protein synthesis is generally initiated by eukaryotic initiation factors (eIFs), which along with p70S6K play critical roles in translational regulation (Ref.1). During mRNA translation, eukaryotic initiation factor 4E (eIF4E) (the m7GTP cap-binding protein) binds to eIF4G (a scaffolding subunit) and eIF4A (an ATP-dependent RNA helicase) to form active eIF4F complex.  eIF4F complex binds to the 7-methyl-GTP cap structure present at the 5’ termini of all eukaryotic mRNAs and recruit the ribosome near the 5’ terminus of mRNA. PABP (Poly (A)-Binding Protein) also play an important role in the recruitment of mRNAs to ribosomes[..]

The ERBB (Erythroblastic Leukemia Viral Oncogene Homolog) or EGF (Epidermal Growth Factor) family of transmembrane RTKs (Receptor Tyrosine Kinases) plays an important role during the growth and development of a number of organs including the heart, the mammary gland, and the central nervous system. In addition, ERBB overexpression is associated with tumorigenesis of the breast, ovaries, brain, and prostate gland. The ERBB family includes four members, EGFR (EGF Receptor)/ERBB1/HER1 (Heregulin-1), ERBB2/HER2 (Heregulin-2), ERBB3/HER3 (Heregulin-3), and ERBB4/HER4 (Heregulin-4).Two of the family members, ERBB1 and ERBB2, are involved in the development of many types of human cancer. All ERBBs have in common an extracellular ligand-binding domain, a single[..]

ERBB4 (Erythroblastic Leukemia Viral Oncogene Homolog-4) is a 180-kDa transmembrane RTK (Receptor Tyrosine Kinase) that regulates cell proliferation and differentiation. The ERBB4 is a member of the EGFR (epidermal growth factor receptor) subfamily of transmembrane RTKs. ERBB4 is expressed in several tissues, mainly heart, mammary gland and the central nervous system. ERBB4 and its ligands have important roles in normal cardiovascular and neural development, differentiation of the mammary gland, and in pathological conditions, such as heart diseases and cancer (Ref.1).ERBB4 can be activated by at least seven members of EGF-related peptide growth factors: betacellulin, epiregulin, HB-EGF (heparin-binding EGF-like growth factor) and the neuregulins (NRG-1, NRG-2, NRG-3,[..]

Killer lymphocytes are key players in the effector arm of the immune response that eliminate cells infected with intracellular pathogens and transformed tumor cells. Killer cells in both adaptive and innate immunity-T cells (CTLS) and natural killer (NK) cells, respectively, use the same basic mechanisms for destroying their targets, although they are triggered by distinct receptors and the expression of cytotoxic granules is constitutive in NK cells, but regulated in T cells. Release of the contents of cytotoxic granules into the immunological synapse formed between the killer cell and its target cell is important for immune elimination of viruses, intracellular bacteria, and tumors. Granzyme-A (GzmA), a tryptase and B (GzmB), serine protease, are the most abundant[..]

NF-KappaB (Nuclear Factor-KappaB) is a heterodimeric protein composed of different combinations of members of the Rel family of transcription factors. The Rel/ NF-KappaB family of transcription factors are involved mainly in stress-induced, immune, and inflammatory responses. In addition, these molecules play important roles during the development of certain hemopoietic cells, keratinocytes, and lymphoid organ structures. More recently, NF-KappaB family members have been implicated in neoplastic progression and the formation of neuronal synapses. NF-KappaB is also an important regulator in cell fate decisions, such as programmed cell death and proliferation control, and is critical in tumorigenesis (Ref.1).NF-KappaB is composed of homo- and heterodimers of five members[..]

Interleukin 3 (IL3) is a T cell-derived glycoprotein involved in cell proliferation, survival and differentiation. It regulates haemopoiesis, the formation of blood cells in the body. IL3, also called multi-CSF (multi-lineage colony stimulating factor), is produced by T cells and mast cells, after activation with mitogens or antigens. It was first isolated from murine bone marrow cells and is also believed to be expressed in neurons and astrocytes of the hippocampus, suggesting an important role in central nervous system (Ref.1). It signals through interactions with cell surface receptors.    IL3 receptor (IL3R) is composed of two polypeptide chains, a unique alpha subunit and a common Beta subunit IL3RB (the common beta chain), which is shared by[..]

PKR (Protein kinase-R) is a ubiquitously expressed serine-threonine kinase that has been implicated as a signal integrator in translational and transcriptional control pathways.  PKR mediate apoptosis induced by many different stimuli, such as LPS (Lipopolysaccharides), IFN-Gamma (Interferon-Gamma), cytokines, growth factor, viral infection, or serum starvation.  PKR activity is regulated by external signals, which act on proteins, which interact with PKR. Among the proteins identified so far are p58, a cellular protein, K3L, the product of a gene of vaccinia virus,  PACT  (Protein Activator Of Interferon-Induced Protein Kinase) and p67, an interferon-induced glycoprotein (Ref.1). Human PKR is a 68 kDa with a 20 kDa N-terminal dsRBD[..]

Complement is a complex system containing more than 30 various glycoproteins present in serum in the form of components, factors, or other regulators and/or on the surface of different cells in the form of receptors. It is a highly sophisticated host defence system designed to destroy pathogens. Once the complement system is activated, a chain of reactions involving proteolysis and assembly occurs, resulting in destruction of the membranes of pathogens. The cascade up to the cleavage of C3 (Complement component 3), which plays a central role in the complement system, is called the activation pathway. There are three categories of complement pathway; the classical pathway, alternative pathway and lectin pathway (Ref.1).The recently discovered lectin pathway (also called[..]

Tumor necrosis factor (TNF) is a pro-inflammatory cytokine with the capacity to induce apoptosis. It is enriched in the tumor microenvironment, promotes tumor growth and subverts innate immune responses to cancer cells. TNF is the best studied member of the TNF superfamily. TNF-alpha can bind to two related receptors, TNF receptors 1 and 2 (TNFR1 and TNFR2), which are also used by other, similar ligands. By binding to TNFR1 and TNFR2, TNF activates distinct signaling pathways important for cell proliferation, cell death and immune responses (Ref.1 and 2). TNFR1 is constitutively expressed in most cell types, whereas TNFR2 is typically restricted to certain subpopulations of immune cells such as CD4+ or CD8+ T cells and a few other cell types such as oligodendrocytes[..]

Lactose (or D-Lactose) is a disaccharide composed of Galactose (or Galactose) and Glucose (or D-Glucose). It occurs only in milk. It is the primary carbohydrate in milk of most species. Lactose is synthesized in mammary glands. Two Glucose molecules are required for each Lactose molecule synthesized. One Glucose is converted to UDP-Glucose (Uridine Diphosphate-Glucose), which in turn is converted to one UDP-Galactose (Uridine Diphosphate-Galactose) by GALE (UDP-Galactose-4-Epimerase) (Ref.1). Another Glucose molecule is used for Lactose synthesis without modification. Glucose passes across the Golgi apparatus membrane into the Golgi apparatus lumen by GLUT1 (Glucose Transporter-1). The presence of GLUT1 on the Golgi apparatus membrane apparently is specific to the[..]

Unsaturated fatty acids are Beta-oxidized in the normal pathway as far as possible. However, polyunsaturation or unsaturation at odd positions produces a molecule that the major pathways cannot utilize as a substrate. To solve this problem, a number of enzymes exist in the peroxisome to convert these molecules to appropriate substrates which can be shuttled into the normal pathway. Peroxisomes are capable of oxidizing a variety of substrates including polyunsaturated Enoyl-CoA esters. The Beta-Oxidation of unsaturated Enoyl-CoA esters in peroxisomes, and also in mitochondria, is not just chain-shortening but also involves the metabolizing of pre-existing carbon-to-carbon double bonds. In addition to the enzymes of the Beta-Oxidation spiral itself, this metabolism[..]

Anthrax is a severe, although rather rare, infectious disease that is caused by the Gram-positive, spore-forming bacterium Bacillus anthracis. The infectious form is the spore and the major virulence factors of the bacterium are its poly-Gamma-D-glutamic acid capsule and the tripartite anthrax toxin. The discovery of the anthrax toxin receptors in the early 2000s has allowed in-depth studies on the mechanisms of anthrax toxin cellular entry and translocation from the endocytic compartment to the cytoplasm. There are three forms of anthrax disease defined by the route of spore entry into the body: cutaneous, gastrointestinal, and inhalational anthrax. Early studies showed that spores are phagocytosed by resident macrophages and dendritic cells, which may serve as a[..]