PKA (Protein Kinase-A) is a second messenger-dependent enzyme that has been implicated in a wide range of cellular processes, including transcription, metabolism, cell cycle progression and apoptosis. Known modulators of PKA activity include factors that either activate or inhibit AC (Adenylate Cyclase), resulting in an increase or decrease in cAMP (Cyclic Adenosine 3',5'-monophosphate) levels. The enzyme occurs naturally as a four-membered structure with two regulatory (R) and two catalytic (C) subunits. Four genes encode the R subunits (RI-Alpha, RI-Beta, RII-Alpha and RII-Beta), and three encode the C subunits (C-Alpha, C-Beta and C-Gamma). Although there are major differences in the tissue distribution, biochemical and physical properties of the R subunit isoforms,[..]

Despite tremendous diversities in their expression, cellular activities in virtually all cell types are regulated by common intracellular signaling systems, and calcium is one important ubiquitous intracellular messenger, controlling a diverse range of cellular processes, such as gene transcription, muscle contraction and cell proliferation. In response to adequate stimuli, [Ca2+]i (Intracellular Ca2+ concentration) increases, oscillates and decreases, leading to the activation, modulation and termination of cell function. Numerous channels and pumps allow this particular cation to enter and exit cells and move between the cytosol and intracellular stores(Ref.1).    When calcium signaling is stimulated in a cell, Ca2+ enters the cytoplasm from one[..]

Progress in the eukaryotic cell cycle is driven by oscillations in the activities of CDKs (Cyclin-Dependent Kinases). CDK activity is controlled by periodic synthesis and degradation of positive regulatory subunits, Cyclins, as well as by fluctuations in levels of negative regulators, by CKIs (CDK Inhibitors), and by reversible phosphorylation. The mammalian cell cycle consists of four discrete phases: S-phase, in which DNA is replicated; M-phase, in which the chromosomes are separated over two new nuclei in the process of mitosis. These two phases are separated by two so called “Gap” phases, G1 and G2, in which the cell prepares for the upcoming events of S and M, respectively.The different Cyclins, specific for the G1-, S-, or M-phases of the cell cycle,[..]

The extended growth potential of cancer cells is critically dependent upon the maintenance of functional telomeres, which are specialized chromosomal DNA-protein structures in the terminal regions of eukaryotic chromosomes (Ref.1). In order to divide, a normal cell has to replicate the entire DNA in its chromosomes. But normal cells have difficulty in copying the last few bases on the telomere. As a result, the telomere shortens with each round of DNA replication and cell division and as a cell ages, the telomere keeps shortening until it reaches a finite length. At that point cells stop dividing and this halt in growth is triggered by a gene p53 that is activated in response to DNA damage. A telomere that becomes too short no longer protects the chromosome from DNA[..]

BRCA1(Breast Cancer Susceptibility Protein-1) is a versatile protein that links DNA damage sensing and DDR effectors. BRCA1 interacts with tumour suppressors, DNA repair proteins and cell cycle regulators through its various functional domains and thereby has diverse roles in multiple DNA repair pathways (particularly HR, NHEJ and SSA (single-strand annealing)) and in checkpoint regulation. BRCA1 contains an amino-terminal RING domain that has E3 ubiquitin ligase activity (which catalyses protein ubiquitylation) and a BRCT(BRCA1 C-Terminal) domain that facilitates phospho-protein binding.BASC (BRCA1-Associated Genome Surveillance Complex), a super complex of BRCA1, is key to recognizing and repairing DNA damage. This complex includes tumor suppressors and DNA damage[..]

Unlimited replicative potential and widespread genomic disarray are among the most common characteristics exhibited by human cancer cells. Although several distinct molecular pathways regulate specific aspects of each of these phenotypes, specialized chromosomal terminal structures, termed telomeres act as essential regulators of both cell life span and chromosomal integrity (Ref.1).Telomeres are dynamic DNA-protein complexes that cap the ends of linear chromosomes, preventing detrimental chromosome rearrangements and defending against genomic instability and the associated risk of cancer. Telomeres shorten every time a cell divides because of incomplete DNA replication and DNA end processing. When telomere length reaches a critical point, cells stop dividing and[..]

Androgens are recognized as genotropic inducers of a number of physiological functions mainly associated with the development of sexual characteristics. Androgens promote the growth and differentiation of prostate cells through ligand activation of the AR (Androgen Receptor) (Ref.1&2). The AR, upon activation by Androgens, mediates transcription of target genes that modulate growth and differentiation of prostate epithelial cells. AR signaling is crucial for the development and maintenance of male reproductive organs including the prostate gland (Ref.3). The majority of serum Androgens is complexed with the plasma glycoprotein SHBG (Sex Hormone-Binding Globulin). The plasma protein SHBG binds to a receptor SHBGR (Sex Hormone-Binding Globulin Receptor) on cell[..]

Vegetative yeast cells respond to environmental cues by activating signal transduction pathways that enable them to mount the appropriate physiological response. Each of the cues is dealt with by distinct signaling mechanisms to cause the appropriate response to a given stimulus. In the budding yeast Saccharomyces cerevisae, there are at least five MAP kinase (Mitogen-Activated Protein Kinase) cascades. MAPK cascades are conserved signaling modules that regulate responses to diverse extracellular stimuli, developmental cues and environmental stresses. A MAPK is phosphorylated and activated by a MAPKK (MAPK Kinase), which is activated by an upstream protein kinase, MAPKK kinase. Each pathway is initiated by a distinct upstream regulator and individual MEKK-MEK-MAPK[..]

MPs (Metalloproteinases) play a key role in the responses of cells to their microenvironment. By effecting proteolytic degradation or activation of cell surface and ECM (Extracellular Matrix) proteins they can modulate both cell-cell and cell-ECM interactions, which influence cell differentiation, migration, proliferation and survival. Both secreted and membrane bound forms of metalloproteinases have been implicated in pericellular proteolysis, including the MMPs (Matrix Metalloproteinases), the adamalysin-like proteinases with both metalloproteinase and disintegrin-like domains (ADAMs and their counterparts that have a thrombospondin-1-like domain, ADAM-TSs) and the Astacins (Ref.1). MMPs are endopeptidases belonging to the metzincin super family, which depend on the[..]

Apoptosis, necroptosis, and pyroptosis are the three major ways of PCD(programed cell death) following virus infection. Among them, apoptosis is the most extensively investigated PCD during viral infection. Apoptosis elicited by virus infection has both negative and positive influence on viral replication.Apoptosis is triggered by two distinct signaling pathways, namely the intrinsic and extrinsic pathways(Ref.1).The intrinsic apoptotic pathway is elicited by a wide range of intracellular stress conditions, including cytokine deprivation, DNA damage, oxidative stress, cytosolic Ca2+ overload and endoplasmic reticulum stress whereas the extrinsic apoptotic pathway is activated by extracellular stress stimulation that is sensed and triggered through activation of death[..]

Most aging individuals die from atherosclerosis, cancer, or dementia; but in the oldest old, loss of muscle strength resulting in frailty is the limiting factor for an individual's chances of living an independent life until death. Three hormonal systems show decreasing circulating hormone concentrations during normal aging: (i) estrogen (in menopause) and testosterone (in andropause), (ii) dehydroepiandrosterone and its sulphate (in adrenopause), and (iii) the growth hormone/IGF1 axis (in somatopause). Physical changes during aging have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Science recognizes aging as a disease that can be reversed to a large degree by increasing GH (Growth[..]

Endotoxin LPS (Lipopolysaccharide) is a component of the outer membrane of Gram-negative bacteria that potently promotes the activation of macrophages and microglia cells, which are important sensors of infection by bacteria, fungi, and viruses, in both the periphery and the CNS (Central Nervous System). There are several known LBP (LPS-Binding Proteins) present on macrophage membranes, including CD14, CD11b/18, and TLR (Toll-like Receptors). TLRs are mammalian homologs of the Drosophila Toll receptor and are involved in initiating innate immune defense against bacteria and fungi. CD14 lacks a transmembrane domain and is unable to initiate signals on its own. Thus, the TLR4 has emerged as a potential signaling partner for LPS/CD14 interactions(Ref.1).The key downstream[..]