Proteomics: a strategy to understand the novel targets in protein misfolding and cancer therapy.
Proteins carry out important functions as they fold themselves. Protein misfolding occurs during different biochemical processes and may lead to the development of diseases such as cancer, which is characterized by genetic instability. The cancer microenvironment exposes malignant cells to a variety of stressful conditions that may further promote protein misfolding. Tumor development and progression often arises from mutations that interfere with the appropriate function of tumor-suppressor proteins and oncogenes. These may be due to alteration of catalytic activity of the protein, loss of binding sites for effector proteins or alterations of the native folded protein conformation. Src family kinases, p53, mTOR and C-terminus of HSC70 interacting protein (CHIPs) are some examples associated with protein misfolding and tumorigenesis. Molecular chaperones, such as heat-shock protein (HSP)70 and HSP90, assist protein folding and recognize target misfolded proteins for degradation. It is likely that this misfolding in cancer is linked by common principles, and may, therefore, present an exciting possibility to identify common targets for therapeutic intervention. Here we aim to review a number of examples that show how alterations in the folding of tumor-suppressor proteins or oncogenes lead to tumorigenesis. The possibility of targeting the targets to repair or degrade protein misfolding in cancer therapy is discussed.
Nagaraj
Nagathihalli S
NS
Department of Surgery, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN-37232, USA. nagaraj.nagathihalli@vanderbilt.edu
Singh
Om V
OV
Merchant
Nipun B
NB
D000970:Antineoplastic Agents; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017510:Protein Folding; D040901:Proteomics / Q000379:methods*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics
D000970:Antineoplastic Agents; D025521:Tumor Suppressor Proteins