Chaperoning signaling pathways: Molecular chaperones as stress-sensing 'heat shock' proteins

Department of Biochemistry, Molecular Biology and Cell Biology, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.
Journal of Cell Science (Impact Factor: 5.43). 08/2002; 115(Pt 14):2809-16.
Source: PubMed


Heat shock proteins interact with multiple key components of signaling pathways that regulate growth and development. The molecular relationships between heat shock proteins, various signaling proteins and partner proteins appear to be critical for the normal function of signal transduction pathways. The relative levels of these proteins may be important, as too little or too much Hsp70 or Hsp90 can result in aberrant growth control, developmental malformations and cell death. Although the functions of heat shock proteins as molecular chaperones have been well characterized, their complementary role as a 'stress-induced' proteins to monitor changes and alter the biochemical environment of the cell remains elusive. Genetic and molecular interactions between heat shock proteins, their co-chaperones and components of signaling pathways suggest that crosstalk between these proteins can regulate proliferation and development by preventing or enhancing cell growth and cell death as the levels of heat shock proteins vary in response to environmental stress or disease.

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Available from: Ellen Nollen, Apr 17, 2014
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    • "HSPs have a critical role in the recovery of cells from stress and in cytoprotection by preventing the irreversible aggregation of stress-denatured proteins and aiding in their refolding into native, functional states. The 70-kDa family is considered the most prominent eukaryotic family of stress proteins and several isoforms exist including the constitutively expressed and the heat-inducible Hsp70, whereas Hsp90 is one of the most abundant cytosolic proteins in eukaryotes (Csermely et al. 1998; Mayer and Bukau 2005; Nollen and Morimoto 2002; Pratt and Toft 2003). It is generally accepted that HSPs protect organisms from the detrimental effects of heat and possibly other environmental stressors including various chemicals, heavy metals, oxidative stress, and desiccation and that stress tolerance depends on the synthesis of HSPs (Bahrndorff et al. 2009; Feder and Hofmann 1999; Kregel 2002; Lindquist 1986; Somero 1995). "
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    • "The classification depends on their molecular weight such as Hsp100, Hsp90, Hsp70, Hsp60 and as well as the family of small Hsp's (Kristensen et al., 2004; Calloni et al., 2012). They are associated with signalling molecules and steroid receptors through the establishment of Hsp70 and Hsp90 (Ellen et al., 2002). "
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    • "These signaling pathways and genes include molecular chaperone encoding genes, genes involved in the unfolded protein response, Mitogen-Activated Protein Kinase (MAPK) and Growth Arrest and DNA Damage 45 (GADD45) signaling pathways (Yang et al., 2009). The Heat Shock Protein (HSP) pathway is a major molecular chaperone signaling pathway, the activation of which has been identified as one of immediate molecular responses to various types of environmental stress, including alcohol, heat, heavy metals and viral infection (Nollen and Morimoto, 2002; Hashimoto-Torii et al., 2011, 2014). Our recent study using knockout mice of Heat shock factor 1 (Hsf1), a canonical transcription factor that controls transcription of Hsp genes revealed that activation of this signaling is required to reduce the risk of cortical malformation, such as heterotopias and small size of the cortex, upon prenatal exposure to various types of environmental stress, thereby reducing susceptibility to epilepsy (Hashimoto-Torii et al., 2014). "
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