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Beschreibung

Cyclic AMP-responsive element-binding protein 3-like protein 2 (UniProt Q8BH52, also known as cAMP-responsive element-binding protein 3-like protein 2) is encoded by the Creb3l2 (also known as Bbf2h7, C530025K05Rik, SCIRR69) gene (Gene ID 208647) in murine species. Creb3l2/Bbf2h7 belongs to the old astrocyte specifically induced substance (OASIS) family of ER-resident transcription factors that function as ER stress transducers. OASIS members are ER transmembrane proteins that possess both a transcription-activation domain and a basic leucine zipper (bZIP) domain. Upon initial activation through regulated intramembrane proteolysis (RIP), OASIS family members are transported from the ER to the Golgi apparatus. Sequential cleavage by site-1 protease (S1P) and site-2 protease (S2P) releases the N-terminal fragment, which then translocates to the nucleus and activates the transcription of target genes. Under normal conditions, cellular BBF2H7 and OASIS levels are low due to degradation via the ubiquitin-proteasome pathway as a result of constant E3 ubiquitin ligase HRD1- (HMG-CoA reductase degradation 1-) mediated ubiquitination. ER stress is shown to disrupt their interaction with HRD1, resulting in enhanced stability of BBF2H7 and OASIS and an upregulation of their target genes.