In response to Retinoic Acid (a metabolite of Vitamin-A (all-trans-Retinol), which affects gene transcription), target genes are regulated by two families of nuclear receptors, the RARs (Retinoic Acid Receptors) and the RXRs (Retinoid X Receptors) that bind as RAR/RXR heterodimers to response elements located in their promoters. The all-trans-Retinoic Acid, the Carboxylic Acid form of Vitamin-A is of biological significance since it is predominant under most physiological situations and explains all of the biological effects of Vitamin-A (Ref.1). Biologically active ligands for the RARs include all-trans-Retinoic Acid, 9-cis-Retinoic Acid among others, yet circulating levels of 9-cis-Retinoic Acid are much lower than those of all-trans-Retinoic Acid and the[..]

ERK5 (also known as the BMK1 (Big MAP Kinase-1)) is an atypical MAPK that can be activated in vivo by a variety of stimuli, including Serum, Growth factors including EGF (Epidermal Growth Factor), NGF (Nerve Growth Factor) and BDNF (Brain-Derived Neurotrophic Factor), GPCRs (G-Protein Coupled Receptors), Lysophosphatidic Acid, Neurotrophins and Phorbol ester and some Cellular stress such as Oxidative and Osmotic Shock. MAPK (Mitogen Activated Protein Kinase) cascades play important roles in many cellular processes including cell proliferation, differentiation, survival and apoptosis. They are also important for many physiological functions in several systems, including in developmental, immune and neuronal systems. At least 12 isoforms of MAPKs exist in mammalian[..]

Glioblastoma Multiforme (GBM) is biologically aggressive neoplasms which have an elevated, often aberrant, proliferative capacity with a diffuse pattern of brain invasion. It is the most malignant Astrocytic tumor, composed of poorly differentiated neoplastic astrocytes. The World Health Organization (WHO) grading system classifies Gliomas into Grades I-IV based on the degree of malignancy, as determined by histopathological criteria. In the Central Nervous System (CNS), Grade-I Gliomas generally behave in a benign fashion and might even be circumscribed, whereas Grade-II, Grade-III and Grade-IV Gliomas are malignant and diffusely infiltrate throughout the brain. Glioblastoma Multiforme falls under the Grade-IV category. Glioblastoma Multiforme or the WHO Grade-IV[..]

ABC (ATP-binding cassette) transporters are a large superfamily of integral membrane proteins involved in the cellular export or import of a wide variety of different substances, including ions, lipids, cyclic nucleotides, peptides, and proteins. ABC transporters are systemically classified into eight subfamilies by sequence similarity, i.e., ABCA (ABC1), ABCB (MDR/TAP), ABCC (MRP/CFTR), ABCD (ALD), ABCE (RNAseLI/OABP), ABCF (GCN20), ABCG (White) and ANSA subclass. In general, the transmembrane part of ABC transporters contains a polar channel formed by two homologous domains, each usually consisting of five (uptake transporters) or six (efflux transporters) transmembrane alpha-helices (Ref.1 & 2). Typically, ABC proteins are relatively specific for a[..]

AMLs (Acute Myeloid Leukemias) are characterized with chromosomal translocations resulting in the formation of fusion proteins. Understanding PML (Acute Promyelocytic Leukemia Inducer) function has become an area of intense research because of its involvement in the pathogenesis of APL (Acute Promyelocytic Leukemia), a distinct subtype of Myeloid Leukemia. In the vast majority of APL case studies, the PML gene (on Chromosome-15) fuses to the RAR-Alpha gene (Retinoic Acid Receptor-Alpha) (on Chromosome-17) as a consequence of reciprocal and balanced chromosomal translocations. In the t(15;17) chromosomal translocation, which is specific for APL, PML is found in a reciprocal translocation with the RAR-Alpha resulting in the formation of PML-RAR-Alpha and RAR-Alpha-PML[..]

Vitamin A and its analogs, collectively termed retinoids, have a profound effect on cell growth, differentiation, apoptosis, and morphogenesis. Retinol, the lipid-soluble vitamin A, is an absolute requirement for normal growth, vision and differentiation of epithelial tissues in mammals. Retinol must be obtained directly through dietary intake, but may also be derived in its provitamin A forms obtained through dietary carotenoids (Ref.1 and 2). Retinoids bind to six distinct nuclear receptors in mammals and regulate the expression of target genes. The Retinoic Acid Receptors (RARs) and Retinoid X Receptors are among the most intensely studied nuclear hormone receptors. RARs are ligand-controlled transcription factors that function as heterodimers with RXRs to regulate[..]

The nuclei of all eukaryotic cells contain three different RNA Polymerases, designated I, II and III. Like the DNA polymerase that catalyzes DNA replication, RNA Polymerases catalyze the formation of the phosphodiester bonds that link the nucleotides together to form a linear chain. The RNA polymerase moves stepwise along the DNA, unwinding the DNA helix just ahead of the active site for polymerization to expose a new region of the template strand for complementary base-pairing. In this way, the growing RNA chain is extended by one nucleotide at a time in the 5’-to-3’ direction. The substrates are nucleoside triphosphates (ATP, CTP, UTP, and GTP); as for DNA replication, a hydrolysis of high-energy bonds provides the energy needed to drive the reaction[..]

GAs (Gibberellins) are members of a large family of Diterpenoid compounds, which are essential for a number of processes, including Gene Expression in Cereal Aleurones, Seed Germination, Elongation, Growth, and Flowering. During the last four decades, Barley Aleurone has been a valuable system for studying GA regulation of gene expression. After germination, GAs are released from the Embryo into the Endosperm, triggering the expression of a number of genes encoding Hydrolytic enzymes in Aleurone cells. Many of these Hydrolytic enzymes, which include Alpha-Amylase, Proteases, and Cell Wall–degrading enzymes, are secreted and are responsible for digestion of the stored reserves in the starchy endosperm. The Signal transduction events leading from the Receptor to[..]

The GAs (Gibberellic Acids or Gibberellins) phytohormones play important roles in plant growth and development, promoting seed germination, elongation growth and reproductive development. GA is important for processes including seed germination, stem growth, and flower and fruit development. Gibberellins are modified in the endoplasmic reticulum and cytosol until they reach their biologically-active form. The gibberellins are named GA1 through GAn in order of discovery. Gibberellic acid, which was the first gibberellin to be structurally characterized, is GA3. There are currently 136 GAs identified from plants, fungi and bacteria.GAs is widespread and so far ubiquitous in flowering (Angiosperms) and non-flowering (Gymnosperms) plants as well as ferns. GA mediates[..]

ABA (Abscisic Acid) is a plant hormone that plays important role during many phases of the plant life cycle, including seed development and dormancy, embryo maturation, cell division and elongation, and in plant responses to various environmental stresses such as drought, salinity, cold, pathogen attack and UV radiation. However, despite the name, it does not appear to control Abscission directly; the presence of ABA in Abscising organs reflects its role in promoting senescence and/or stress responses, the processes preceding Abscission. ABA is a sesquiterpenoid (C15H20O4) with one asymmetric, optically active Carbon atom at C-1'f. The naturally occurring form is S-(+)-ABA; the side chain of ABA is by definition 2-cis,-4-trans. Trans, trans-ABA is biologically[..]

Atherosclerosis is a chronic disease, the prevalence of which has increased steadily as the population ages. Vascular injury is believed to be critical initiating event in pathogenesis of spontaneous atherosclerosis. Economic development and urbanization have promoted habits of diet rich in saturated fat and diminished physical activity, which favors atherosclerosis. Traditionally two types of atherosclerosis are described, spontaneous and accelerated. Accelerated atherosclerosis mainly occurs in patients after heart transplant, CABG (coronary artery bypass graft), and PTCA (percutaneous transluminal coronary angioplasty) [Ref.1]. The normal artery contains three layers. The inner layer, the tunica intima, is lined by a monolayer of endothelial cells that is in contact[..]

The CD1 (Thymocyte Antigen CD1) antigen presentation system presents lipid and glycolipid antigens to effector T-Cells, which have diverse roles in Antimicrobial responses, Antitumor immunity and in regulating the balance between Tolerance and Autoimmunity. CD1, a conserved family of MHC (Major Histocompatibility Complex)-like glycoproteins in mammals, specializes in capturing lipid rather than peptide antigen for presentation to T-lymphocytes (Ref.1). The CD1 family consists of five isoforms of non-polymorphic lipid antigen-presenting molecules, which are classified into two groups: Group-I (CD1A, CD1B, CD1C, and CD1E) and Group-II (CD1D), based on similarities between nucleotide and amino acid sequences. Topologically, they resemble the classical peptide[..]