Cyclic AMP-responsive element-binding protein 3-like protein 2 (CREB3L2)

Cyclic AMP-responsive element-binding protein 3-like protein 2 (CREB3L2) is a member of the basic leucine zipper (bZIP) transcription factor family, specifically one of the ER-resident CREB3 family proteins[1][2][5]. Under endoplasmic reticulum (ER) stress, CREB3L2 undergoes regulated intramembrane proteolysis; its N-terminal fragment is released and translocates to the nucleus, where it drives the expression of key genes such as SEC23A in chondrocytes to promote ER-Golgi trafficking and secretion of matrix proteins, supporting cartilage development and cell survival[1][2][5]. Pathologically, chromosomal translocations creating FUS–CREB3L2 fusion proteins are characteristic of low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma, where fusion activates aberrant transcriptional programs linked to tumorigenesis[1][2]. CREB3L2 is also activated downstream of oncogenic signaling (e.g., RAS/MAPK) in certain tumors, promoting cell survival by regulating anti-apoptotic pathways (e.g., ATF5-MCL1 axis)[1]. CREB3L2 is thus a key regulator of secretory pathway and cell survival, and serves as a molecular marker for certain sarcomas but is not currently a direct therapeutic target[1][2][5].

Other names

BBF2H7cAMP responsive element binding protein 3 like 2B-ZIB transcription factorFUS/BBF2H7 proteinTCAG_1951439basic transcription factor 2BBF2 human homolog on chromosome 7

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