Title : How do we tackle the resurgent drug-resistant tuberculosis?
Speaker : Prof. V. Nagaraja, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore
Date : 08/01/2020, 5:30 PM , C.V Raman Hall, Second Floor.
Inositol pyrophosphates, a class of water soluble inositol phosphates found in all eukaryotic cells, consist of pyrophosphate and monophosphate moieties around an inositol ring. The most abundant inositol pyrophosphate, 5-diphosphoinositol pentakisphosphate (5PP-IP5 or 5-IP7), is synthesised from inositol hexakisphosphate (IP6) by IP6 kinases (IP6Ks), and participates in a variety of cellular functions. Inositol pyrophosphates can transfer their beta-phosphate to a pre-phosphorylated serine residue, resulting in serine pyrophosphorylation. We are interested in examining how pyrophosphorylation of specific proteins regulates their function, and in turn modulates cellular homeostasis. We have demonstrated that 5-IP7-mediated pyrophosphorylation of RNA polymerase I regulates ribosome synthesis in budding yeast. In mammalian cells, we have shown that pyrophosphorylation of the oncoprotein MYC regulates its stability, and pyrophosphorylation of the motor protein dynein is essential for vesicle trafficking. While protein pyrophosphorylation was discovered more than a decade ago, the impact of this novel modification on diverse cellular pathways is only now being appreciated. Our current knowledge of the importance of protein pyrophosphorylation, and recent advances in understanding the mechanism of this important yet under-appreciated posttranslational modification will be discussed.