XRK3F2 is an inhibitor of p62 (Sequestosome-1)-ZZ/ domain.
The presence of XRK3F2 during MM-preOB co-cultures prevents Runx2 suppression at both d0 and d4. Furthermore, XRK3F2 blocks MM-induced upregulation of Gfi1. XRK3F2 blocks the induction of Gfi1 mRNA in BMSC in both treatment conditions. In contrast, XRK3F2 prevents both MM1.S CM and TNFα plus IL7-mediated Runx2 suppression. Further, the pro-inflammatory and myeloma pro-survival factor IL6 mRNA is also reduced by XRK3F2 treatment. In addition, XRK3F2 also prevents TNFα-mediated upregulation of Gfi1 and rescues inhibition of Runx2 in MC4 preOB. XRK3F2 prevents MM-induced GFI1 occupancy at the Runx2-P1 promoter. XRK3F2 treatment significantly rescues the H3K9ac levels at Runx2 in MM patient hBMSC and XRK3F2 can rescue early steps in osteogenesis[1].
[1]. Adamik J, et al. XRK3F2 Inhibition of p62-ZZ Domain Signaling Rescues Myeloma-Induced GFI1-Driven Epigenetic Repression of the Runx2 Gene in Pre-osteoblasts to Overcome Differentiation Suppression. Front Endocrinol (Lausanne). 2018 Jun 29;9:344.