A Novel Sumoylation-independent Mechanism of SUMO-1 Function: SUMO-1 Induces Ubiquitin-independent Proteasomal Degradation of CP2c

초록

Covalent conjugation of the small ubiquitin-related modifier-1 (SUMO-1) is known to modify activities of a variety of substrate proteins. Here, we report a novel, sumoylation independent SUMO-1 function, whereby SUMO-1 directly binds to the target CP2c protein without covalent conjugation, and induces degradation of target protein via proteasomal pathway in the nucleus. SUMO-1 was initially identified along with Ubc9 and PIAS1 in a yeast two-hybrid screen for CP2c-interacting proteins. The direct physical interaction between the bait (CP2c) and the prey (SUMO-1, Ubc9, and PIAS1) proteins was confirmed both in vitro and in vivo. Among CP2c binding proteins, only SUMO-1 significantly reduced the protein level and transcriptional activity of CP2c. Surprisingly, SUMO-1 mediated CP2c degradation occured by the proteasomal pathway and requires Glycine residues at the C-terminus of SUMO-1, but does not involve sumoylation or ubiquitination. Furthermore, CP2c interacts with SUMO-1 independently from the PML body using two regions of CP2c (39-134 aa and 306-415 aa). Taken together, our data demonstrate a novel sumoylation-independent mechanism of SUMO-1 modulation.