SENP6 and RNF4 act antagonistically to maintain CENP-I homeostasis. CENP-I conjugation to poly–SUMO-2/3 is mediated by SUMO activating (sE1) and conjugating (sE2) enzymes and perhaps one or more SUMO ligases (sE3). This allows it to be ubiquitinated by RNF4 and degraded by proteasomes. SENP6 deconjugates the SUMO-2/3 chains on CENP-I, preventing its degradation in this manner. By spatially or temporally restricting the activity of SENP6 in this pathway, it should be possible to restrict the stability of CENP-I and prevent its inappropriate accumulation at noncentromeric regions. NAC proteins are shown as hexagons, whereas CAD proteins are depicted as ovals (Foltz et al., 2006). Different colors indicate putative subcomplexes identified through biochemical studies (Okada et al., 2006; Cheeseman et al., 2008).