Abstract IA06: Recycling Myc to survive stress

Missexpression of Myc family members has been linked to numerous abnormalities ranging from developmental defects to cancer. Indeed there is considerable evidence that Myc expression is controlled at every level of gene regulation, including protein degradation. Recently we found that Myc is targeted by calcium-dependent cytosolic proteases from the calpain family. Unlike proteasomal degradation resulting in complete protein destruction, calpain mediated proteolysis leads to partial cleavage of substrates. While regulated calpain activity is essential for embryonic development and terminal differentiation, aberrant calpain levels and activity have been correlated with tumor development and metastasis.We found that upon calpain cleavage, the C-terminus of Myc is degraded, while an N-terminal segment of about 300 aminoacids is preserved and gives rise to Myc-nick. The removal of the C-terminus of Myc, which is essential for nuclear translocation and to binding to DNA and to Max, renders Myc-nick transcriptionally inactive and cytoplasmically localized. The conversion of Myc into Myc-nick is significantly enhanced in cancer cells exposed to stress conditions such as hypoxia and nutrient deprivation. Importantly, we found that Myc-nick expression increases the survival of colon cancer cells following nutrient deprivation, hypoxia, and treatment chemotherapeutic agents such as etoposide, cisplatin and imatinib. Myc-nick expressing cells display an increase in autophagy and treatme...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Myc and Metabolism - Metabolomics: Oral Presentations - Invited Abstracts Source Type: research