The Regulation of Pml Degradation by Sentrin-Specific Protease 2

Project: A - Government Institutionb - Ministry of Science and Technology

Description

Among the post-translation modifications, SUMO modification is emerging as an important post-translational control of protein functions. While many cellular factors are modified by SUMO, very little is known about the mechanism underlying SUMO-elicited protein-protein interaction and regulation. In the past few years, my studies were focused on the role of Daxx protein in Smad4-mediated transcriptional repression and revealed that Daxx can function as SUMO reader via its SUMO-interacting motif (SIM) in a SUMO-dependent manner. We further demonstrated that Daxx SIM can be phosphorylated with CK2 kinase for altering its binding properties. In addition, we recently found that SENP2, a SUMO protease, could bind to SUMO polychain and consist of two putative SIMs within its catalytic domain. We hypothesize that SENP2 regulates substrate desumoylation in part via its SIM binding to SUMO moiety of sumoylated substrates. Because PML is a substrate of SENP2 and its sumoylation is associated with protein stability, we will explore whether SENP2 regulate PML sumoylation, protein stability and cellular functions via SENP2 SIM. In this proposal, we will first characterize the SUMO binding affinity and specificity of SENP2 SIM by biochemical assays in vitro and in vivo. Because MEK/ERK cascade controls the PML ubiquitination and degradation, we will further characterize whether the SENP2 facilitates PML ubiquitination and degradation by desumoylation of PML. Moreover, the role of SENP2 SIM in PML ubiquitination and degradation will be addressed. Finally, we will explore the importance of SENP2 in PML-dependent cell migration. Altogether, our proposed studies will not only determine how SUMO protease recognizes substrate for desumoylation but also elucidate a possible regulatory mechanism for PML stability and associated cell migration modulated by SENP2.
StatusFinished
Effective start/end date11/1/127/31/13

Keywords

  • PML stability
  • SUMO protease
  • SUMO-interacting motif