TRAF6 and myelodysplastic syndrome: However, prolonged stimulation of TLR can result in hematopoietic stem and progenitor cell (HSPC) dysfunction.297 TRAF6, a TLR effector molecule with ubiquitin ligase activity, is significantly upregulated in MDS, ubiquitinating HNRNPA1 and thereby regulating the exon 2 exclusion of Arhgap1, which has been shown to regulate the self-renewal and differentiation of long-term hematopoietic stem cells.298 Furthermore, the activation of the Rho family GTP-binding protein, Cdc42 leads to hematopoietic defects in HSPCs expressing TRAF6.299