Cyclic AMP-responsive element-binding protein 3 (CREB3)

Cyclic AMP-responsive element-binding protein 3 (CREB3) is a membrane-bound transcription factor of the endoplasmic reticulum (ER) that belongs to the basic leucine zipper (bZIP) superfamily[3][5]. It is activated by regulated intramembrane proteolysis (RIP) in response to ER or Golgi stress: CREB3 translocates to the Golgi, where cleavage by Site-1 and Site-2 proteases releases its N-terminal fragment, which then enters the nucleus to activate specific genes[2][3][4]. CREB3 family members—including CREB3, CREB3L1, CREB3L2, CREB3L3, and CREB3L4—act as key transcriptional regulators in diverse processes such as the unfolded protein response, metabolism, development, immune signaling, and stress adaptation[2][4]. CREB3 can bind to various DNA motifs, including the cAMP response element (CRE), ER stress response element II (ERSE-II), and the unfolded protein response element (UPRE)[2][3]. It is implicated in disease processes including cancer and neurodegenerative disorders due to its central role in maintaining ER homeostasis and regulating essential cellular responses to stress[2][4][5].

Other names

LumanLZIPsLZIP

Not applicable directly, as no drugs are known to target CREB3 specifically; in principle, compounds modulating ER stress pathways or transcription factor activity could alter CREB3 function, but no approved mechanisms specific to CREB3 are documented[2][5].