The Regulatory Network of CREB3L1 and Its Roles in Physiological and Pathological Conditions

Abstract

CREB3 subfamily belongs to the bZIP transcription factor family and comprises five members. Normally they are located on the endoplasmic reticulum (ER) membranes and proteolytically activated through RIP (regulated intramembrane proteolysis) on Golgi apparatus to liberate the N-terminus to serve as transcription factors. CREB3L1 acting as one of them transcriptionally regulates the expressions of target genes and exhibits distinct functions from the other members of CREB3 family in eukaryotes. Physiologically, CREB3L1 involves in the regulation of bone morphogenesis, neurogenesis, neuroendocrine, secretory cell differentiation, and angiogenesis. Pathologically, CREB3L1 implicates in the modulation of osteogenesis imperfecta, low grade fibro myxoid sarcoma (LGFMS), sclerosing epithelioid fibrosarcoma (SEF), glioma, breast cancer, thyroid cancer, and tissue fibrosis. This review summarizes the upstream and downstream regulatory network of CREB3L1 and thoroughly presents our current understanding of CREB3L1 research progress in both physiological and pathological conditions with special focus on the novel findings of CREB3L1 in cancers.

Isorhamnetin inhibits hypertrophic scar formation through TGF-β1/Smad and TGF-β1/CREB3L1 signaling pathways

“…Therefore, examining the key mechanism by which TGF-β1 induces the long-term accumulation of ECM is crucial to inhibiting HS formation. CREB3L1 is a transcription factor that belongs to the CREB/ATF family considered a transmembrane precursor in the endoplasmic reticulum [ 24 ]. CREB3L1 can be activated via cleavage mediated by site-1 protease and site-2 protease during the process of RIP [ 25 ].…”