Frontiers in Structural Biology

Frontiers in Structural Biology

Role of Molecular Chaperones in Structural Folding, Biological Functions, and Drug Interactions of Client Proteins

The book provides an updated panorama of the functional relevance of molecular chaperones in the proper folding of client factors, protein-protein interactions, the regulation of key biological ...
[view complete introduction]

US $
30

*(Excluding Mailing and Handling)



Regulatory Roles for Hsp70 in Cancer Incidence and Tumor Progression

Pp. 1-22 (22)

Taka Eguchi, Benjamin J. Lang, Ayesha Murshid, Thomas Prince, Jianlin Gong and Stuart K Calderwood

Abstract

The HSP70 family of molecular chaperones plays a significant role in cancer. Notably, the inducible protein Hsp72 becomes expressed in many cancers, often to high levels and underlies escape of tumor cells from senescence and increased tumor initiation and metastasis. Examination of database suggests that mutation within the ORFs of HSP70 genes in cancer is relatively rare suggesting a requirement for intact function. At the molecular level, Hsp72 is thought to chaperone key proteins in tumorigenesis and permit their accumulation in the malignant cell. In addition, an important role for Hsp72 in RNA metabolism is emerging, indicating mechanisms potentially involving the RNA binding protein HuR. The existence of multiple HSP70 pseudogenes may also be important for future studies of long non-coding RNA (lncRNA) regulation through this family of chaperones. As the significance of this family of chaperones in cancer emerges, small molecule inhibitors have been developed as future potential cancer pharmaceuticals. We discuss the targeting of individual HSP70 families at key functional domains in the proteins.

Keywords:

Heat shock protein seventy, Structure, Function, Cancer, Growth, Metastasis, Chemical inhibitor, Substrate, Domain, ATPase, Drug.

Affiliation:

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA02115, USA.