Simplified (partial) mechanism for the cytosolic stress response

Slides:



Advertisements
Similar presentations
Metabolism of ganglioside GM2 in GM2 activator-deficient fibroblasts
Advertisements

A: Population frequency histogram of urinary debrisoquine/4-hydroxydebrisoquine ratios after debrisoquine administration to 258 individuals in a healthy.
Genomic organization of the human cathepsin K gene
Simplified view of the cellular RNA and protein quality surveillance or control systems. Stop-codon introductions as well as splice-site variations, resulting.
Simplified view of the cellular RNA and protein quality surveillance or control systems. Stop-codon introductions as well as splice-site variations, resulting.
More detailed view of the process shown in Fig
A, Diagnosis of clinical severity (mild, moderate, severe) of hemophilia is based on in vitro coagulant activity as shown. B, Distribution of severe and.
Spectrum of different types of human gene mutations logged in Human Gene Mutation Database as of September 13, 1998 ( Source: The.
Advantages of isolated liver transplantation before kidney failure over combined liver-kidney transplantation afterwards. Oxalate excretion: Black line.
Morphologic appearance of EH skin. Shown is a semithin section (0
Distribution of diagnoses among the nearly 115,000 cases of lymphoid malignancy diagnosed in There are 5400 cases of acute lymphoid leukemia (ALL),
Distribution of diagnoses among the nearly 115,000 cases of lymphoid malignancy diagnosed in There are 5400 cases of acute lymphoid leukemia (ALL),
IX; formation of sphingolipids, sphingosine is synthesised from L-serine and palmitoyl-CoA. Source: Serine deficiency disorders, The Online Metabolic and.
Proposed model for the structure of ABC1 within the plasma membrane (modified from reference202 ). The two symmetric halves consisting of six membrane-spanning.
Illustration of the origin of tubular cysts
Structure of the A-subunit gene and identified mutations
Light micrographs comparing pycnodysostosis and normal bone
The lymphocyte markers that distinguish the various stages of B-cell differentiation are shown. Markers that are expressed on the cell surface are indicated.
Schematic representation of the DTDST protein
Radiographic appearance of intracranial meningioma in NF2
YAC and BAC cloning systems
The PKD1 and PKD2 gene products are integral transmembrane proteins
Prototypical eukaryotic gene
A section of the cerebellum stained with Sevier-Munger preparation from the brain of a 10-year-old SCA1 patient with 82 CAG repeats who died after 6 years.
Effect of chenodeoxycholic acid feeding on the bilirubin levels of a 10-year-old boy with 3β-hydroxy-Δ5-oxidoreductase/isomerase deficiency. (From Setchell.
Aggregation-mediated passive sorting of secretory and membrane proteins during the biogenesis of a secretory granule in the TGN. (1) The luminal contents.
Urinary excretion (mg/h) of tryptophan derivatives following administration of oral L-tryptophan (about 70 mg per kilogram body weight) administered to.
A hypothetical model of the central apoptotic pathway
Free energy folding landscape for a hypothetical protein
A representation of the DNA damage-induced cell cycle checkpoint pathway in mammalian cells. DNA damage results in accumulation of the p53 protein. Accumulation.
Model depicting the cycling of REP
Relation between the fractional catabolic rate (FCR) for plasma LDL and the number of LDL receptors on fibroblasts in patients with FH. The values for.
Model accounting for the mechanisms linking epipodophyllotoxin therapy, MLL fusion proteins, cell cycle progression, and the relaxation of cell cycle checkpoints,
Two children with LPI. The pictures were taken at the time of diagnosis. A, Child 12 years old. B, Child 6 years old. Note the prominent abdomen, hypotrophic.
RhoGEFs activate a Rho protein GTPase by catalyzing the exchange of GDP for GTP. A variety of stimuli lead to the activation of Rho protein family members.
Evolution of the ubiquitous α-, β-, and γ-crystallins and their structure. Details are described in the text. The α-crystallins are related to heat-shock.
Mechanism of NO synthesis
A comparison of normal cardiac anatomy (A) and the pathology of hypertrophic cardiomyopathy (B). Hypertrophic cardiomyopathy causes cardiomegaly (570 g;
Structure and mutation spectrum of BRCA1
Orofacial dyskinesia in a patient with Huntington's disease
OCTN2 mRNA in fibroblasts from normal controls and patients with primary carnitine deficiency. PolyA RNA isolated from fibroblasts of normal controls or.
Mechanism of NO synthesis
Insulin secretion rates during graded intravenous glucose infusions administered to 6 MODY-2 subjects with glucokinase (GCK) mutations and 6 control subjects.
Photosensitive skin lesions on the face of a child with C4 deficiency
Expression of mutant human P5C dehydrogenase alleles in yeast
Karyotype of glioblastoma
The renin-angiotensin-aldosterone system
Hydrolysis of membrane-associated ceramide by acid ceramidase in the presence of saposins and bis(monoacylglycero)phosphate (BMP) in the acidic lysosomal.
MRI contrast-enhancement and progression of X-ALD
Role of molecular chaperones in the importation of polypeptides into the mitochondrial matrix. Recently synthesized cytoplasmic polypeptides are kept in.
Key structural elements of p53 DNA binding
Electrophoregram profiles showing the 35delG mutation of CX26 (GJB2) in an individual with recessively inherited hearing loss, and in his heterozygous.
Corneal opacity in a heterozygote observed by slit-lamp microscopy
FISH of glioblastoma. This interphase nucleus from a glioblastoma contains three chromosome 7 centromere signals (dark) and one centromere 10 signal (light).
A model of the protein C activation complex
Young female with OCA1B. The hair was white at birth
A model for the role of ALK-1 and endoglin in normal angiogenesis
Overview of the TGF-β signaling pathway
Schematic representation of p53 molecule
Structural features of the p53 gene and its encoded protein
The effects of apo E alleles on various lipoprotein parameters
Hepatic glucose production as a function of fasting plasma glucose levels. These studies involved the same individuals who were studied in Fig
Basic algorithm for cancer risk assessment that employs gene testing.
Schematic working model of the hepatic microsomal glucose-6-phosphatase system. ER = endoplasmic reticulum. This model is not meant to represent the actual.
Detection of XIST RNA in interphase cells from a normal male, a normal female, and a 49,XXXXX female by RNA fluorescence in situ hybridization. Male.
Structure and mutation spectrum of BRCA2
Composite megalosaccharide proposed for blood group substance
Complete chemical structures of the neutral glycosphingolipids that accumulate in Fabry disease. A, Globotriaosylceramide, the major accumulated substrate.
The PBDs can be caused by defects in peroxisomal matrix protein import or peroxisome membrane synthesis. Immunofluorescence microscopy shows that human.
The mammalian unfolded protein response pathway
Presentation transcript:

Simplified (partial) mechanism for the cytosolic stress response Simplified (partial) mechanism for the cytosolic stress response. Under stress conditions, native proteins and--to a larger degree--proteins containing missense sequence variations as well as modifications will be denatured. According to the simplified "chaperone sequestration" hypothesis, chaperones--particularly Hsp90 and Hsp70--leave the inactivated heat shock factor HSF1 and bind to the unfolded conformations. The unmasked HSF1 will trimerize and be transferred to the nucleus, where it is activated before binding to heat-shock elements of a number of heat-shock genes. Some of these genes code for chaperones, which try to compensate for the functional decrease in the amounts of chaperones available for protection of proteins against aggregation as well as against insults from misfolded proteins on vital cellular functions, such as the mitochondrial function. If this is compromised, reactive oxygen species (ROS) may be formed. In addition to the compensating stress response that induces the production of protecting chaperones, the proteasome--which is the most important proteolytic system in the cell--will try to eliminate misfolded and modified proteins. Depending on the balance between rate and amounts of unfolding and the compensating/eliminating mechanisms, the cell will survive or proceed into apoptosis. Source: Protein Folding and Misfolding: The Role of Cellular Protein Quality Control Systems in Inherited Disorders, The Online Metabolic and Molecular Bases of Inherited Disease Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: https://ommbid.mhmedical.com/DownloadImage.aspx?image=/data/books/971/ch13_1fg16.png&sec=62640652&BookID=971&ChapterSecID=62640472&imagename= Accessed: November 03, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved