Volume 2 of the Asian Youth Journal of Biology.
Investigating the Role of HSF1 in the Folding of Oncogenic ALK Fusion Proteins
by Camille Esther Arcinas and Thilo Hagen
Asian Youth Journal of Biology 2014, 2:1-16 [PDF of article]
Lay Abstract. Cancer is a consequence of the activation of proto-oncogenes and inactivation of tumor suppressor genes. ALK is a proto-oncogene that becomes activated in non-small cell lung cancer and other cancers through fusion with other proteins. Such fusion proteins are the result of chromosomal rearrangements. Fusion of ALK to proteins such as EML4 or KIF5B leads to constitutive ALK dimerization and activation. As a result, cell proliferation and transformation of cells into cancer cells is promoted. Inhibitors of ALK have proved highly effective to treat ALK fusion protein dependent tumors. However, the tumors eventually develop drug resistance. Hence, it is necessary to develop additional therapeutic approaches. In this study we investigate whether targeting the folding of the ALK fusion proteins is a viable therapeutic strategy. This is because ALK fusion proteins are non-natural proteins and hence may not readily take up their correct three-dimensional conformation. Our results are in agreement that these proteins are indeed unstable and prone to misfolding. We also determined whether targeting the transcription factor heat shock factor 1 (HSF1) might be a suitable therapeutic approach to target ALK fusion protein expression. HSF1 is known as a master regulator of protein folding related cellular processes. However, our results suggest that targeting HSF1 alone may not be a viable approach. Future studies should be directed to identify other regulators of ALK fusion protein folding.
Superoxide Dismutase Switch in Breast Cancer: A Potential Target for Cancer Therapy
by Pallavi Panda
Asian Youth Journal of Biology 2014, 2:17-20 [PDF of article]
Lay Abstract. Superoxide Dismutases (SODs) are enzymes involved in converting toxic superoxide radical into either molecular oxygen or hydrogen peroxide in biological systems. A switch from Superoxide Dismutase (SOD) 2 to SOD1 activity in breast cancer cells functions as a key adaptive mechanism to protect the mitochondria from increased oxidative damage. This switch is critical for cancer cells to maintain proliferative growth. Importantly, inhibition of SOD1 could serve as a potential anti-cancer therapy.
Non-Enzymatic Acetylation in Alkaline Environments
by Adrian Tan Hong Ji
Asian Youth Journal of Biology 2014, 2:21-23 [PDF of article]
Lay Abstract. The mechanism behind the acetylation reactions in mitochondria has remained a mystery for a long time, until now. A recent study by Wagner and Payne (2013) revealed that mitochondrial proteins are acetylated non-enzymatically and such a mechanism has far reaching consequences in human diseases.
A Coupled Understanding of UCP2 Function and Metabolic Reprogramming
by Lim Han Qi, Hans
Asian Youth Journal of Biology 2014, 2:24-27 [PDF of article]
Lay Abstract. Uncoupling Proteins are a family of integral proteins found on the inner mitochondrial membrane and are thought to uncouple fuel oxidation and ATP synthesis in mitochondria. Uncoupling Protein-2 (UCP2) is a member of this family. Intriguingly, increase in level of UCP2 expression is associated with metabolic reprogramming and the Warburg effect (switch from reliance on citric acid cycle to glycolysis for energy production) in cancer cells. A recent study by Vozza and co-workers (2014) revealed that UCP2 catalyses the export of C4 metabolites from the mitochondrial matrix into the cytosol. This new understanding of the function of UCP2 explains how it contributes to metabolic reprogramming and is of immense value in understanding the progression of cancer and other metabolic disorders, and ultimately in developing drugs to treat them.