Sirtuins: implications in cancer and aging

Biochemistry, Biophysics, Molecular Biology

Metabolic and energy homeostasis play a vital role in governing the cellular pathways. It is important to note that molecular factors involved in these processes are implicated in life-style disorders (diabetes/ obesity), aging and age related diseases (cancer/ neurodegeneration).

One of the proteins that directly link metabolic inputs to various molecular events within a cell is Sir2, which was initially identified in yeast as an NAD-dependent HDAC. Sirutins (Sir2-like proteins) play a vital role in cell survival, DNA damage response, cellular differentiation and aging. We use flies, mice and cell culture systems to elucidate the molecular mechanisms regulated by sirtuins. Importantly, we investigate their functions in metabolic and energy homeostasis and also study their role during aging and age-related diseases such as cancer, diabetes and obesity.

Publications

1. Ramachandran D, Roy U, Ghosh S, Garg S, Pathak S, Kolthur-Seetharam U (2011) Glucose dependent changes in mir-9 transcription regulate the NAD-dependent deacetylase Sirt1 in insulin secreting beta-cells. FEBS Journal 278(7):1167
2. Ghosh S, George S, Roy U, Ramachandran D, Kolthur-Seetharam U (2010) NAD: A master regulator of transcription. Biochimica Biophysica Acta 1799: 681
3. Kolthur-Seetharam U, Teerds K, de Rooij DG, Wendling O, McBurney M, Sassone-Corsi P, Davidson I (2009) The histone deacetylase SIRT1 controls male fertility in mice through regulation of hypothalamic-pituitary gonadotropin signaling. Biology of Reproduction 80: 384
4. Kolthur-Seetharam U, Martianov I, Davidson I (2008) Specialization of the general transcriptional machinery in male germ cells. Cell Cycle 7: 3493
5. Kolthur-Seetharam U, Françoise D, McBurney MW, de Murcia G, Sassone-Corsi P (2006) Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage. Cell Cycle 5: 873
6. Kolthur-Seetharam U, Monaco L, Loury R, Ménissier-de Murcia J, de Murcia G, Sassone-Corsi P (2005) Inhibition of Aurora-B kinase activity by poly (ADP-ribosylation) in response to DNA damage. Proceedings of National Academy of Sciences USA 102: 14244