protein degradation process, will be discussed along with the Ubiquitin Ligase, a major player in the mechanism. Ubiquitination is a post-translational modification where ubiquitin, an 8kDa protein that is highly conserved in eukaryotes, is attached to a substrate protein (Lu et al., 2008). Ubiquitin is attached to a targeted protein through a sequential cascade which involves E1 activating, E2 conjugating, and E3 ligase enzymes. This ubiquitin tagging is necessary for many cellular processes, including
Angelman Syndrome is a rare genetic disorder characterized by neurological and developmental issues. Dr. Harry Angelman discovered the syndrome in 1965. It was formerly called “Happy Puppet Syndrome” due to the clinical features possessed by those affected. Dr. Angelman observed those affected as appearing normal upon birth but eventually showing signs of development disabilities. Angelman Syndrome mainly targets the nervous system and can be detected in infants as early as six months. Typically
regarded as the most prominent tumor suppressor gene [1]. P53 is a gene which signals apoptosis (programmed cell death) if a cell cannot be repaired due to an extensive amount of damage. As stated in the textbook, p53 regulation occurs by an E3 ubiquitin-protein ligase known as MDM2 [1]. "Controlling the controller" is a statement that describes the molecular interaction where the presence of MDM2 targets the p53 for proteosome via degradation. With three main checkpoints in cell cycle, the literature states
CREB-1 (Ca2+/cAMP response element binding protein-1) Ca2+/cAMP response element binding (CREB-1) protein is a transcription factor that regulates cell growth, homeostasis and survival. A TM phosphorylates CREB at Ser111 in response to IR. This, in turn, triggers CK-2 dependent phosphorylation of Ser108 and CK1 dependent phosphorylatio~ ofSer114 and Ser117. The phosphorylation of Ser 114 and Ser 117 by CK1 renders CREB permissive for ATM dependent phosphorylation at Ser121 (Shanware et al., 2007)
2010). Recent genetic and biochemical study revealed that mutations in a unique PXX repeat region of UBQLN2 which is one of ubiquitin like protein family are causative in ALS. The different mutations of UBQLN2 are present in the typical skein-like inclusion which is a hallmark of ALS pathology. In detailed functional relevance of ubiquitin like domain (UBL) and ubiquitin association domain (UBA) of UBQLN2 still need further elucidation, degradation of UPS reporter slowed in neuroblastoma cells
MUTANT HUNTINGTIN PROTEIN AGGREGATION AND PROTEASOMAL DISFUNCTION AN INSILICO STUDY 1. INTRODUCTION 1.1 Huntingtons Disease Huntington’s disease (HD) is a progressive autosomal dominant neurodegenerative genetic disorder. HD was originally named Huntington’s chorea after Dr.George Huntington, an American physician who first gave a detailed note on the symptoms and course of the disease in 1872.Recently the name has been changed to Huntington’s disease to emphasize the fact that chorea is not the
Angelman Syndrome (AS) is a neurodevelopmental disorder, which is caused by mutations or deletions of the UBE3A gene inherited from the maternal allele. This gene encodes the protein E3 ubiquitin ligase. UBE3A is expressed biallelically in majority of tissues but in most neurons the maternal allele is solely expressed. In 1965 Dr. Harry Angelman an English pediatrician first described Angelman syndrome. At the time of discovery Dr. Angelman named the disorder “happy puppet syndrome” this was due
Plants like many eukaryotic composed organisms have the ability to detect and protect themselves against microorganisms known as pathogens. Plant fossils have recorded that land plant’s existence was established 480 million years ago, but molecularly, plant evolution began 700 million years ago. Molecular interaction with microbes and other organisms gave the shape and structure of plants, giving us an idea that microbes also evolve according to its host. Plants lack mobility depriving themselves
Centrosomes are cytoplasmic organelles which contain two centrioles (mother and daughter centriole) positioned perpendicular to each other. Each centriole is a cylindrical structure, ~100-150 nm in diameter and 100- 400 nm in length, made up of nine microtubule triplets (singles or doublets in some cells) (Delattre and Gönczy, 2004). The centrosome is surrounded by pericentriolar material (PCM) which helps in nucleating microtubules. The PCM contains pericentrin, centrin, γ-tubulin ring complexes
crosslink repair. In the process of DNA repairing, the interstrand crosslinks is recognized by the complex of two proteins, FAAP24 and FANCM. These proteins participate in substrate binding and enable recruitment of the FA core complex. This core has E3 ligase activity and can monoubiquitinate (addition of o... ... middle of paper ... ...d DNA damage response pathway. EMBO J. 26: 2104–2114. Nalepa G, Enzor R, Sun Z, Marchal C, Park SJ, Yang Y, Tedeschi L, Kelich S, Hanenberg H and Clapp DW. 2013. Fanconi
Simian virus 40 (SV40) is a monkey virus that was introduced into the human population by contaminated poliovaccines. The vaccines were produced in SV40 infected monkey cells between 1955 and 1963. The site of latent infection in humans is not known but the presence of SV40 in urine suggests the kidney as a possible site of latency. SV40 is a small DNA virus that is studied extensively because it is able to transform and immortalize multiple cell types (Ozer 2000, Saenz-Robles et al. 2001). Polyoma
Y chromosome, the smallest chromosome of the karyotpe, is one of the two sex chromosomes. In 1905, Nettie Stevens identified that Y chromosome is a sex-determining chromosome, while conducting one study of the mealworm Tenebrio molitor. He also proposed that chromosomes always existed in pairs. In 1890 Hermann Henking discovered that Y chromosome was the pair of the X chromosome. All chromosomes normally appear to take on a well defined shape during mitosis when seen under microscope. This shape
Kaylee Laub Von Hippel-Lindau Syndrome Disease Overview Von Hippel-Lindau (VHL) syndrome is a rare autosomal dominant genetic disorder that occurs in about 1 in every 35,000 births (Mahon, Suzanne M., 2012). The first reports on VHL syndrome were published in medical literature about a century ago where Treacher Collins and Eugene von Hippel were the first to describe families that had blood-vessel tumor development in the retina (Kaelin, William G., 2002). Later on Arvind Lindau, a neuropathologist
Functional genomics is an area of study within molecular biology which attempts to analyse genetic products, in order to understand the function and interaction of genes, and the proteins produced by them. It is a genome-wide method used under different environmental conditions and the DNA function can be deciphered through a combination of genes, proteins and transcripts. The new approach provides geneticists with the possible answers of understanding how genes interact with one another and analysing