Dipeptidyl peptidase III interaction with SH2 domain-containing protein 3C – possible link between oxidative stress response and cell migration
Dipeptidyl peptidase III (DPP III) is a zinc metallopeptidase that sequentially cleaves off dipeptides from the amino-termini of 3 to 10 residue long peptides, ubiquitously present in organisms from bacteria to human. It has assumed role in the final stages of protein turnover in the cell, and in the regulation of blood pressure and pain. DPP III is also involved in the regulation of Nrf2/KEAP1 signalling pathway mediated by the competitive binding to KEAP1 protein that leads to the release of Nrf2 transcription factor and the activation of the oxidative stress response. In the search for other interactors of DPP III by SILAC-MS approach, SH2 domain-containing protein 3C (SH2D3C) was identified as a putative interactor. The interaction was confirmed on overexpressed proteins by several biochemical methods. SH2D3C is one of the three members of the NSP family of proteins which contain both SH2 domain, RasGEF-like domain, and a proline/serine rich region in between. SH2D3C and the other two members of the same family (SH2D3A and BCAR3) serve as adaptor or scaffolding proteins that control cell migration by integrating growth factor and integrin signalling, however, the exact mode of their action is still unknown. We propose to confirm the interaction between endogenous DPP III and SH2D3C and investigate the effect of each protein on the function of the other by the overexpression and knock-down of the genes, respectively, determine the affinity of the binding by biophysical methods, and use molecular modelling to predict the likely binding sites. The results of the proposed investigations will enable better understanding of the role of DPP III in the signalling pathways related to SH2D3C in human cells and vice versa. Considering that the cell migration control and Nrf2/KEAP1 signalling pathways are frequently dysregulated in cancer, the results of the proposed research might offer new possibilities for cancer biomarker identification and treatment.
PARTICIPATION IN CONFERENCES AND WORKSHOPS:
Mihaela Matovina participated at 45th FEBS Congress (virutal), 03-08/07/2021, Ljubljana, Slovenija, poster presentation
Ana Tomašić Paić, Lea Barbarić and Mihaela Matovina participated at workshop about Preparative chromatography, 16-17/12/2021., BioCentar, Zagreb, Croatia
Mihaela Matovina participated at The 25th IUBMB Congress, the 46th FEBS Congress and the 15th PABMB Congress (The Biochemistry Global Summit), 9-14/7/2022, Lisbon, Portugal, poster presentation
Mihaela Matovina i Lea Barbarić participated at the International Congress of the Croatian Society of Biochemistry and Molecular Biology HDBMB22: FROM SCIENCE TO KNOWLEDGE, 28/09-01/10/2022, Brela, poster presentation MM, poster presentation LB
Lea Barbarić participated at EMBL workshop "Protein quality control in downstream processes", 29/11-02/12/2022, Heidelberg, Germany. The workshop consisted of short lectures about the production and quality control of proteins by the use of biophysical techniques like DSL, MST, ITC, SEC-MALS, nanoDSFm cryo-EM etc., followed by hands-on workshop aimed at gaining practical experience with the aforementioned techniques and the analysis of own samples.
Ana Tomašić Paić participated at 4th ISFMS—Biochemistry, Molecular Biology and Druggability of Proteins (ISFMS2022), 06-09/09/2022, Florence, Italy, poster presentation
Marina Oskomić participated at BenBedPhar Training School 2023 organizired in scope of COST action CA20121 „Bench to Bedside transition for Pharmacological regulation of NRF2 in non communicable diseases“, 26-30/06/2023, Smolenice Castle, Slovakia, poster presentation
Lea Barbarić and Marina Oskomić participated at Summer school MedILS School in Bioinformatics Part I (21-25/08/2023) i Part II (16-20/10/2023) at The Mediterranean Institute for Life Sciences (MedILS), Split, Croatia.
Mihaela Matovina participated at COST action CA20121 „Bench to Bedside transition for Pharmacological regulation of NRF2 in non communicable diseases“ scientific meeting, 12-13/10/2023, Grazu, Austria with the lecture „The effect of DPP3 mutation found in cancer on the KEAP1-NRF2 Signaling Pathway“, lecture
M. Matovina et al. Identification of SH2 Domain-Containing Protein 3C as a Novel, Putative Interactor of Dipeptidyl Peptidase 3, Int. J. Mol. Sci. 2023, 24(18), 14178; https://doi.org/10.3390/ijms241814178