[en] Highlights: • mIκBNS is degraded rapidly by proteasome without ubiquitylation. • N-terminal PEST sequence is responsible for the unstable nature of mIκBNS. • PEST sequence is not critical for nuclear localization of mIκBNS. • There is single bona fide NLS at the C-terminus of mIκBNS. - Abstract: Negative regulatory proteins in a cytokine signaling play a critical role in restricting unwanted excess activation of the signaling pathway. At the same time, negative regulatory proteins need to be removed rapidly from cells to respond properly to the next incoming signal. A nuclear IκB protein called IκBNS is known to inhibit a subset of NF-κB target genes upon its expression by NF-κB activation. Here, we show a mechanism to control the stability of mIκBNS which might be important for cells to prepare the next round signaling. We found that mIκBNS is a short-lived protein of which the stability is controlled by proteasome, independent of ubiquitylation process. We identified that the N-terminal PEST sequence in mIκBNS was critical for the regulation of stability

[en] SUMOylation regulates a variety of cellular processes, including control of transcriptional activities of nuclear receptors. Here, we present SUMOylation of orphan nuclear receptor, RORα by both SUMO-1 and SUMO-2. SUMOylation of RORα occurred on the 240th lysine residue at the hinge region of human protein. PIAS family members, PIASxα, PIAS3, and PIASy, increased SUMOylation of RORα, whereas SENP2 specifically removed SUMO from RORα. SUMOylation-defective mutant form of RORα exhibited decreased transcriptional activity on RORα-responsive promoters indicating that SUMOylation may positively regulate transcriptional function of RORα.