Research Paper Volume 11, Issue 23 pp 11268—11313

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

Figure 7. RXFP3 interactome analysis using BioGRID extracted interactomes and GEN3VA extracted signatures, a first indication of a role in Aging. Using the BioGRID database (http://www.thebiogrid.org) the interacting proteins of several known oxidative stress and DNA damage proteins were extracted, and assembled into specific interactomes. (A) Here we show the number of overlapping proteins between the unstressed RXFP3 interactome (Ctrl; black) versus the stressed interactomes (combined both the response to oxidative stress and DNA damage, Stress; Red) and the interacting proteins of DNA damage response/repair proteins (MDC1, H2AFX, BRCA1, PRKDC, TP53, MDM2) and oxidative stress proteins (SOD1, G3BP1, SIRT1). We see that while the RXFP3 interactome in control conditions already shows overlap, this overlap is considerably increased under stress. (B) When we assemble the interactomes of the oxidative stress and DNA damage proteins separately, Ox Stress and DDR, respectively, we again see this greater overlap for the RXFP3 “stress” interactome. When this was repeated for three proteins unrelated to oxidative stress, DNA damage or aging (other), we did not see this overlap. (C) Next, GEN3VA (http://amp.pharm.mssm.edu/gen3va/) was used to extract protein signatures pertaining to aging, which is of most interest to us, schizophrenia, of which we hypothesize RXPF3 might be a controlling factor, and as a negative control we extracted protein signatures for aortic aneurysm, where we suspect RXFP3 is not associated with at all. The overlap was visualized using InteractiVenn (http://www.interactivenn.net). (D) The overlapping proteins were then visualized in a bar chart, showing the large differences between “ctrl” and the “stress” interactomes of RXFP3. In addition, we see nearly no overlap with the signature for aneurysm, a decent overlap for schizophrenia, and a large overlap with aging. This data not only indicates the large differences between RXFP3 in control versus RXFP3 in stress conditions, but that RXFP3 possible plays an important role in oxidative stress, DNA damage response and aging.