Chaperoning the guardian of the genome. The two-faced role of molecular chaperones in p53 tumor suppressor action

Organized networks of heat shock proteins, which possess molecular chaperone activity, protect cells from abrupt environmental changes. Additionally, molecular chaperones are essential during stress-free periods, where they moderate housekeeping functions. During tumorigenesis, these chaperone netwo...

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Bibliographic Details
Published in:Biochimica et biophysica acta. Reviews on cancer 2018-04, Vol.1869 (2), p.161-174
Main Authors: Wawrzynow, Bartosz, Zylicz, Alicja, Zylicz, Maciej
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - therapeutic use
Carcinogenesis
Chemoresistance
Drug Resistance, Neoplasm
Gene Expression Regulation, Neoplastic
Heat shock proteins
Heat Shock Transcription Factors - genetics
Heat Shock Transcription Factors - metabolism
Heat-Shock Proteins - genetics
Heat-Shock Proteins - metabolism
Humans
Molecular Chaperones - antagonists & inhibitors
Molecular Chaperones - genetics
Molecular Chaperones - metabolism
Molecular Targeted Therapy
Mutant p53 gain of function
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Signal Transduction
Tumor suppressor p53
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary:Organized networks of heat shock proteins, which possess molecular chaperone activity, protect cells from abrupt environmental changes. Additionally, molecular chaperones are essential during stress-free periods, where they moderate housekeeping functions. During tumorigenesis, these chaperone networks are extensively remodeled in such a way that they are advantageous to the transforming cell. Molecular chaperones by buffering critical elements of signaling pathways empower tumor evolution leading to chemoresistance of cancer cells. Controversially, the same molecular chaperones, which are indispensable for p53 in reaching its tumor suppressor potential, are beneficial in adopting an oncogenic gain of function phenotype when TP53 is mutated. On the molecular level, heat shock proteins by unwinding the mutant p53 protein expose aggregation-prone sites leading to the sequestration of other tumor suppressor proteins causing inhibition of apoptosis and chemoresistance. Therefore, within this review therapeutic approaches combining classical immuno- and/or chemotherapy with specific inhibition of selected molecular chaperones shall be discussed.
ISSN:0304-419X
1879-2561
DOI:10.1016/j.bbcan.2017.12.004