Encyclopedia of Cancer

2017 Edition
| Editors: Manfred Schwab

Molecular Chaperones

  • Marissa V. Powers
  • Paul Workman
Reference work entry
DOI: https://doi.org/10.1007/978-3-662-46875-3_3810

Definition

Proteins that transiently interact with nascent polypeptide substrates to protect them from misfolding and aggregation. They also have an important role in helping to achieve the native conformation of the newly synthesized protein without forming part of the final folded product. The molecular chaperone  HSP90 is responsible for the stability and activity of a range of oncogenic client proteins and is a target for cancer drugs.

Characteristics

Proteins are mediators of a vast array of biological processes, and their activity is dependent on obtaining their correct three-dimensional conformation. It has been widely accepted from in vitro folding experiments that the formation of the native state is a spontaneous process that is dictated by the amino acid sequence of the protein. However, protein folding in vivo is complicated by the crowded cellular environment which naturally favors protein misfolding and aggregation. Under certain conditions, aggregation may lead to the...

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Notes

Glossary

ATPase

Enzymes that use ATP hydrolysis to yield energy to drive an energetically unfavorable reaction.

Proteasome

A protein degradation complex which can digest a variety of proteins into short polypeptides and amino acids.

Ubiquitination

A posttranslational modification involving the attachment of ubiquitin molecules to specific lysine residues in target proteins. Often this modification acts as a tag for the rapid cellular degradation of the protein by the proteasome.

WD40 repeat

A poorly conserved motif consisting of a repeat sequence containing 40–60 amino acids, which usually contains a Trp-Asp (WD). Several consecutive repeats fold into a domain structure known as a β-propeller in which each section of the structure is a four-stranded β-sheet.

References

  1. Butler LM, Ferraldeschi R, Armstrong H et al (2015) Maximizing the therapeutic potential of HSP90 inhibitors. Mol Can Res; 13(11):1445–51Google Scholar
  2. Kim YE, Hipp MS, Bracher A et al (2013) Molecular chaperone functions in protein folding and proteostasis. Annu Rev Biochem 82:323–355PubMedCrossRefGoogle Scholar
  3. Lopez T, Dalton K, Frydman J (2015) The mechanism and function of group II chaperonins. J Mol Biol.11; 427(18): 2919–30Google Scholar
  4. Neckers L, Workman P (2012) HSP90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res 18(1):64–76PubMedPubMedCentralCrossRefGoogle Scholar
  5. Powers MV, Jones K, Barillari C et al (2010) Targeting HSP70: the second potentially druggable heat shock protein and molecular chaperone? Cell Cycle 9(8):1542–1550PubMedCrossRefGoogle Scholar

See Also

  1. (2012) ATPase. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 302. doi:10.1007/978-3-642-16483-5_442Google Scholar
  2. (2012) Biomarkers. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, pp 408–409. doi:10.1007/978-3-642-16483-5_6601Google Scholar
  3. (2012) Chaperonins. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 754. doi:10.1007/978-3-642-16483-5_1047Google Scholar
  4. (2012) J-Domain. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 1926. doi:10.1007/978-3-642-16483-5_3176Google Scholar
  5. (2012) Kinase. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 1943. doi:10.1007/978-3-642-16483-5_3217Google Scholar
  6. (2012) Tetracopeptide repeat TPR domains. In: Schwab M (ed) Encyclopedia of cancer, 3rd edn. Springer, Berlin/Heidelberg, p 3660. doi:10.1007/978-3-642-16483-5_5743Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Cancer Research UK Cancer Therapeutics UnitThe Institute of Cancer ResearchSuttonUK
  2. 2.Cancer Research UK Center for Cancer TherapeuticsThe Institute of Cancer ResearchSuttonUK