cAMP responsive element binding protein 3-like 1 (CREB3L1)

cAMP responsive element binding protein 3-like 1 (CREB3L1) is a membrane-bound transcription factor of the basic leucine zipper family, predominantly localized in the endoplasmic reticulum (ER) membrane under resting conditions. Upon cellular stress (notably ER stress or DNA damage), CREB3L1 undergoes regulated intramembrane proteolysis, releasing its N-terminal transcription factor domain, which translocates to the nucleus and drives expression of genes involved in cell cycle arrest, extracellular matrix remodeling, collagen production, and the unfolded protein response. CREB3L1 is crucial in bone formation, particularly by regulating collagen type I synthesis in osteoblasts, and is also implicated in neurogenesis, endocrine regulation, secretory cell differentiation, and angiogenesis. Mutations in CREB3L1 are causative for osteogenesis imperfecta type XVI, and diverse somatic alterations or fusion events drive the biology of several fibrotic diseases and cancers. If you need specific references or wish to explore targets for drug development in this protein family, the related gene entries and disease contexts in bone biology, fibrotic disorders, or oncology may provide further direction.

Other names

OASISOld astrocyte specifically induced substanceBBF-2 homolog (drosophila)PSEC0238C16DELp11.2DEL16p11.2OI16processed cyclic AMP-responsive element-binding protein 3-like protein 1BBF-2 homologold astrocyte specifically-induced substanceOsteogenesis imperfecta type XVI

For indirect activators (chemotherapeutic agents like doxorubicin): Induction of ER stress leading to regulated intramembrane proteolysis and activation of CREB3L1, which inhibits cell cycle progression via upregulation of p21 and other genes. For bisphosphonates (risedronate, preclinical model): Attenuation of ER expansion and amelioration of osteoblast defects through modulation of CREB3L1 pathway.