image: Figure 1: The molecular chaperone network. Client proteins rely on sequential interactions with chaperones, cochaperones, and chaperonins to fold into an active, native, state. Thus, functional levels of client proteins are tightly regulated by this process. The chaperones, cochaperones, and chaperonins commonly involved in the chaperoning of tumor suppressor proteins are shown; however, the exact number and types of molecular chaperone network members necessary for proper chaperoning is client-specific. Abbreviations: Hsp70: heat-shock protein 70; HOP: Hsp70-Hsp90 organizing protein; TRiC: tailless complex polypeptide 1 ring complex; Hsp90: heat-shock protein 90; Aha1: Activator of Hsp90 ATPase.
Credit: 2024 Heritz et al.
“Focusing on the holistic lifecycle of these proteins reveals commonalities between the widely diverse group of tumor suppressors, which is invaluable to inform therapy development for multiple cancers.”
BUFFALO, NY- October 16, 2024 – A new review was published in Oncotarget's Volume 15 on October 1, 2024, entitled, “Molecular chaperones: Guardians of tumor suppressor stability and function.”
As highlighted in the abstract of this paper, "tumor suppressor" describes a diverse set of genes typically involved in suppressing metastasis, but which can lead to tumorigenesis when loss-of-function mutations occur. Despite the varied structures and functions of tumor suppressor proteins, many share a common regulatory mechanism—they are "clients" of molecular chaperones, and they rely on an intracellular network of chaperones and co-chaperones to maintain their stability. Mutations in tumor suppressors that disrupt proper chaperoning prevent cells from maintaining sufficient protein levels for normal physiological function.
In their review, researchers Jennifer A. Heritz, Sarah J. Backe, and Mehdi Mollapour from SUNY Upstate Medical University and New York VA Health Care in Syracuse, New York, discuss the role of molecular chaperones Hsp70 and Hsp90 in maintaining the stability and functional integrity of tumor suppressors. They also detail the contributions of co-chaperones prefoldin, HOP, Aha1, p23, FNIP1/2, and Tsc1, as well as the chaperonin TRiC, to tumor suppressor stability.
“Overall, it is clear that oncogenesis can result from the dysregulation of tumor suppressor stabilization by chaperones.”
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28653
Correspondence to: Mehdi Mollapour - mollapom@upstate.edu
Keywords: cancer, molecular chaperone, tumor suppressor, renal cell carcinoma, Birt-Hogg-Dubé (BHD) syndrome, TSC syndrome
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Journal
Oncotarget
Method of Research
Systematic review
Subject of Research
Not applicable
Article Title
Molecular chaperones: Guardians of tumor suppressor stability and function
COI Statement
Authors have no conflicts of interest to declare.