Dr Alicja Sznarkowska from ICCVS was awarded PLN 1.78 mln from National Science Centre for the realisation of SONATA project on the “Characterisation of the Function and Regulation of Nrf2 Isoform 2”.
Nrf2 pathway is a key survival and defence pathway in the cell that allows it to return to balance upon exposure to xenobiotic or oxidative stress eg. toxicants or gamma irradiation. Upon stress activation, Nrf2 is derepressed and translocates to the nucleus to induce expression of various detoxifying and antioxidant genes. Such self-protecting responses are desired in tumor cells and Nrf2 pathway was found deregulated and constitutively active in various cancers, including the non-small cell lung cancer (NSCLC).
“Recently we have found that alternative transcription initiation of Nrf2 gene produces isoform shorter of 16 amino acids at the N-terminus, namely Nrf2 isoform 2, which is highly expressed both in normal and cancer lung cells” – says dr Sznarkowska. This Nrf2 isoform does not behave as a full-length form and does not translocate to the nucleus upon stress. “Thus we assume that its role is different to the full-length Nrf2 and in this research we will study what the function of Nrf2 isoform 2 in cells is and how it is regulated. Such transcriptionally defective forms exist in other transcription factors such as p53, p63 and p73 and add another layer of regulation to their pathways. Thus we are thrilled to study how Nrf2 isoform 2 affects the Nrf2 pathway and what is the potential of its targeting in tumors. One of the approach we will use is the isolation of ribosomes to study the amount of isoforms translated under different conditions” – continues dr Sznarkowska.