70-kDa heat-shock proteins

Kiang, J.G., Tsokos, G.C. (1998). Heat shock protein 70 kDa molecular biology, biochemistry and physiology. Pharmacol. Ther. 80 183-201. 

Figure 3. Schematic architecture of mitochondrial protein complexes. A transmembrane channel, called the permeability transition pore (FTP), is formed at the contaa sites between the inner and outer mitochondrial membrane (OM) of the mitochondria. The core components of PTP are the voltage-dependent anion channel (VDAC) in the outer membrane and the adenine nucleotide translocator (ANT) in the inner membrane (IM). VDAC allows diilusion of small molecules (<5 kDa), however ANT is only permeable to a few selected ions and metabolites and is responsible for maintaining the proton concentration gradient (pH) and the membrane elearic potential (A P,J. PTP is sometimes connected to destruction of permeability barrier and loss of the inner membrane potential and eventually results in mitochondrial membrane permeability transition during apoptosis and other specialized forms of cell death. Bax, Bak, Bc1-Xl and Bcl-2 locate in the outer membrane and may regulate the outer membrane permeability. The translocase of the outer membrane (TOM) and the translocase of the inner membrane (TlM) mediate protein import pathway in the mitochondria. Cy-D, cyclophilin D PBR, peripheral benzodiazepine receptor HK, hexokinase mtHSP70, mitochondrial heat shock protein 70.

Wu, B., Williams, G.T., Morimoto, R.I. (1987). Deletion of three protein binding sites in the serum-regulated promoter of the human gene encoding the 70 kDa heat shock protein. Proc Natl. Acad. Sci. USA 84, 2203-2207. 

Zakeri, Z. F., Ponzetto, C., and Wolgemuth, D. J. (1988). Translational regulation of the novel haploid-specific transcripts for the c-abl proto-oncogene and a member of the 70 kDa heat-shock protein gene family in the male germ line. Dev. Biol. 125 417-422. 

Clark CG, Roger AJ (1995) Direct evidence for secondary loss of mitochondria in Entamoeba histolytica. Proc Natl Acad Sci USA 92 6518-6521 Claras MG, Vincens P (1996) Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem 241 779-786 Craig EA, Kramer J, Kosic-Smithers J (1987) SSC1, a member of the 70-kDa heat shock protein multigene family of Saccharomyces cerevisiae, is essential for growth. Proc Natl Acad Sci USA 84 4156-4160... 

Germot A, Philippe H, Le Guyader H (1996) Presence of a mitochondrial-type 70-kDa heat shock protein in Trichomonas vaginalis suggests a very early mitochondrial en-dosymbiosis in eukaryotes. Proc Natl Acad Sci USA 93 14614-14617... 

Spinach CAP79 CAP85 CAP160 Related to 70 kDa heat shock protein Related to LEA and dehydrins C. L. Guy, personal communication... 

Liao, J., Lowthert, L. A., Ghori, N., and Omary, M. B. (1995). The 70-kDa heat shock proteins associate with glandular intermediate filaments in an ATP-dependent manner. / Biol. Chem. 270, 915-922. 

Figure 7.11. The effects of exposure temperature on protein synthetic patterns of isolated gill tissue from specimens of 13°C-acclimated Tegula funebralis. Autoradiographic images illustrate newly synthesized (35S-labeled) proteins of several size classes (molecular mass standards are shown in the left lane). Two specimens from each temperature of incubation are shown. At temperatures above 24°C, synthesis of heat-shock proteins in the molecular mass ranges of 38, 70, 77, and 90 kDa is induced. Hsp synthesis becomes an increasingly large fraction of protein synthesis as exposure temperature increases, and by 38°C, only synthesis of hsp70 is observed. By 39° C, no protein synthesis takes place. (Figure modified after Tomanek and Somero, 1999.)...

A 22-year-old man was found dead in a field. At autopsy, all organs were severely congested. Concentrations of metamfetamine in the heart, urine, and stomach were 0.8, 17, and 6.2 pg/ml respectively. Immunohistochemical tests on skeletal muscle showed lower than normal immunoreactivity of myoglobin, and 70-kDa heat shock protein was positive in the kidney. Because the concentration of metamfetamine in the blood was not lethal, acute intoxication was not deemed to have been the cause of death. Rather, based on the immunohistochemical findings, it was suggested that the patient had died of hyperthermia and metabolic acidosis. The patient s muscular hyperactivity had led to hyperthermia and metabolic acidosis. 

An 18-year-old woman died after taking a single dose of oral metamfetamine. The autopsy showed severe congestion and edema in the lungs. The metamfetamine concentration in blood from the heart was 17 pg/ ml and metamfetamine was also found in the urine and stomach contents. This patient also had reduced concentrations of myoglobin in skeletal muscle, but there was no evidence of 70-kDa heat shock protein in the kidney, in contrast to the previous case. As the concentration of metamfetamine in the patient s heart was above the lethal concentration, she was reported to have died of acute metamfetamine intoxication. 

The family of 70-kDa heat-shock-related proteins is a widespread family of proteins that are essential for normal cell viability and thermotolerance, but whose specific in vivo biochemical functions are not yet well understood. The members of this family that were identified initially had levels of expression substantially enhanced in response to heat shock for example, the seminal observation of heat-inducible 70-kDa proteins in Drosophila was reported by Tissieres and colleagues in 1974. Only later did it become apparent that cells had other homologues, closely related in sequence to the inducible representatives, that were expressed consti-tutively or in a less stringently regulated fashion. As a consequence, the nomenclature by which members of this family have been referred to, i.e., heat-shock proteins (HSPs) or heat-shock-related proteins, has historically inflicted some confusion as to the functions of the proteins. 

Craig, E. A., Kang, P.., and Boorstein, W. (1990). A review of the role of 70 kDa heat shock proteins in protein translocation across membranes. Antonie van Leeuwenhoek 58, 137-146. 

Liberek, K., Skowyra, D., Zylicz, M., Johnson, C., and Georgopoulos, C. (1991b). The Escherichia coli DnaK chaperone, the 70-kDa heat shock protein eukaryotic equivalent, changes conformation upon ATP hydrolysis, thus triggering its dissociation from a bound target protein, y. Biot. Chem. 266, 14491-14496. 

The members of the 70-kDa heat shock protein (hspVO) family perform functions that are essential for cell viability, both under normal and stress conditions. Constitutively expressed hsp70s are thought to be involved in the folding and assembly of newly synthesized proteins, disassembly of oligomeric proteins, protein degradation, and the transport of nascent peptide chains across membranes (l, 2). 

Hsu CC, Davis KM, Jin H, Foos T, Floor E, Chen W, Tyburski JB, Yang CY, Schloss JV, Wu JY (2000) Association of L-glutamic acid decarboxylase to the 70-kDa heat shock protein as a potential anchoring mechanism to synaptic vesicles. J Biol Chem 275 20822-20828. 

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