1,721,021 research outputs found
M96, A ZINC-DEPENDENT MRE BINDING-PROTEIN, MAY BE INVOLVED IN THE ACTIVATION OF MT GENES BY HEAVY-METAL IONS INDUCTION
No full textInteractions of the zinc regulated transcription factor (ZiRF1) with the the mouse MT Ia promoter
No full textEditorial: Homeostatic regulation of protein synthesis, folding and secretion by stress response pathways in eukaryotes
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Regulation Zirf1 and basal SP1 trascription factor MRE-binding activity by transition metals.
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The Endoplasmic Reticulum Unfolded Protein Response in Neurodegenerative Disorders and Its Potential Therapeutic Significance
Full text linkIn eukaryotic cells, the endoplasmic reticulum (ER) is the cell compartment involved in
secretory protein translocation and quality control of secretory protein folding. Different
conditions can alter ER function, resulting in the accumulation of unfolded or misfolded
proteins within the ER lumen. Such a condition, known as ER stress, elicits an integrated
adaptive response known as the unfolded protein response (UPR) that aims to restore
proteostasis within the secretory pathway. Conversely, in prolonged cell stress or
insufficient adaptive response, UPR signaling causes cell death. ER dysfunctions are
involved and contribute to neuronal degeneration in several human diseases, including
Alzheimer, Parkinson and Huntington disease and amyotrophic lateral sclerosis. The
correlations between ER stress and its signal transduction pathway known as the
UPR with neuropathological changes are well established. In addition, much evidence
suggests that genetic or pharmacological modulation of UPR could represent an
effective strategy for minimizing the progressive neuronal loss in neurodegenerative
diseases. Here, we review recent results describing the main cellular mechanisms linking
ER stress and UPR to neurodegeneration. Furthermore, we provide an up-to-date
panoramic view of the currently pursued strategies for ameliorating the toxic effects
of protein unfolding in disease by targeting the ER UPR pathway
The intracellular lectin ERGIC-53 and the molecular basis of the inherited disease combined deficiency of coagulation factors V and VIII
No full textHematologic characterization and analysis of genetic transmission in a case of double heterozygosity Hb Lepore/beta-thalassemia.
No full textSec23a as the key molecular target of ER Stress dependent modulation of COPII assembling G. Amodio1, O. Moltedo1, V. Pecoraro1, P. Remondelli2 1Dipartimento di Farmacia, Univ. of Salerno, Italy 2Dipartimento di Medicina e Chirurgia , Univ. of Salerno, Italy
No full textExit from the Endoplasmic Reticulum (ER) of newly synthesized proteins is mediated by COPII vesicles that bud from the ER at the ER Exit Sites (ERESs). Disruption of ER homeostasis causes accumulation of unfolded and misfolded proteins in the ER. This condition is referred as ER stress. Several evidences suggest a link between the ER stress and the vesicular trafficking within of the early secretory pathway. Previously, we demonstrated that ER Stress rapidly impairs the anterograde transport to the Golgi complex and the formation of COPII vesicles. Sec23a is one of the component of the COPII vesicles coat and its GTPase activating function on Sar1 is one of the key mechanisms of COPII assembly. Interestingly, we found that ER Stress reduces the association to the ER membrane of Sec23a. Concomitantly, FRAP and FLIP analysis of Sec23a revealed that ER stress accelerates its recycling kinetics on ER membrane. The reduced permanence of Sec23a at the ERES could be the mean through which ER Stress modulates COPII assembling and vesicular trafficking. Moreover, we found that Sec23a is mono-ubiquitinated in mammalian cells in two different sites of its second β-barrel domainand that the induction of ER stress reduces the amount of mono-ubiquitinated Sec23a. Noteworthy, this modification is a mono-ubiquitination on two different cysteines of the β-Barrel domain that is implicated in the binding of Sec23a to the ER membrane. Emerging evidences have demonstrated that ubiquitination on cysteines is implicated in many processes including signal transduction and membrane translocation. The regulatory function of cysteine ubiquitination, its localization in the β-Barrel domain and its impairment during ER stress strictly support the idea that Sec23a is the moleculartarget of ER Stress-dependent modulation of vesicular trafficking and that the regulation of Sec23a ubiquitination is the molecular mechanism involved in this phenomena
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