Affinage

CREB3L2

Cyclic AMP-responsive element-binding protein 3-like protein 2 · UniProt Q70SY1

Length
520 aa
Mass
57.4 kDa
Annotated
2026-04-28
43 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CREB3L2 (BBF2H7) is an ER-resident transmembrane bZIP transcription factor that couples secretory load sensing to transcriptional expansion of the vesicular transport machinery. Upon ER stress or physiological secretory demand, CREB3L2 undergoes regulated intramembrane proteolysis by S1P/S2P; the released N-terminal fragment translocates to the nucleus and directly activates CRE/ATF6-element target genes—most critically Sec23a (and Sec24D)—thereby enlarging COPII vesicle capacity for ER-to-Golgi transport of bulky cargoes such as procollagens, proinsulin, and tyrosinase (PMID:17178827, PMID:19767744, PMID:38013154, PMID:41516372). The secreted luminal C-terminal fragment functions as a paracrine ligand that binds Indian hedgehog and Patched-1 to activate Hedgehog signaling in neighboring cells (PMID:24332809, PMID:39792663). Beyond trafficking, nuclear CREB3L2 drives an ATF5–MCL1 anti-apoptotic pathway (PMID:20495567, PMID:22936798), scales translation capacity in secretory cells by binding regulatory genes genome-wide (PMID:31481663), and is itself regulated transcriptionally by Sox9 and androgen receptor, and post-translationally by O-GlcNAcylation, mTORC1-stimulated cleavage, and proteasomal degradation (PMID:24711445, PMID:38013154, PMID:40164587).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2006 High

    The fundamental identity of CREB3L2 as an ER stress-induced, membrane-anchored transcription factor was established, resolving how an ER-resident protein could activate nuclear gene expression: regulated cleavage releases an N-terminal fragment that translocates to the nucleus and binds CRE elements.

    Evidence Biochemical fractionation, reporter assays, siRNA knockdown, and overexpression in neuroblastoma cells

    PMID:17178827

    Open questions at the time
    • Identity of the specific proteases (S1P/S2P) performing the cleavage was not yet demonstrated
    • Physiological target genes downstream of nuclear CREB3L2 were unknown
    • In vivo relevance was untested
  2. 2007 Medium

    Demonstration that full-length CREB3L2 localizes to ER structures while transmembrane-deleted forms are nuclear, and that CREB3L2 activates box-B, ATF6, and CRE sites, clarified the dual-compartment logic of its activation mechanism.

    Evidence Transfection of tagged constructs in NIH3T3 and HEK-293 cells with reporter assays and imaging

    PMID:17117415

    Open questions at the time
    • Endogenous cleavage was not directly shown in these cell types
    • FUS–CREB3L2 fusion context limits generalizability of transcriptional strength comparisons
  3. 2008 High

    Regulated intramembrane proteolysis by S1P and S2P was directly demonstrated for endogenous CREB3L2 in primary thyroid cells, establishing the specific proteolytic mechanism and showing that the nuclear fragment activates transcription independently of cAMP.

    Evidence Reporter assays with EVX1-CRE, Western blot of cleavage intermediates, and primary thyroid cell overexpression

    PMID:18757431

    Open questions at the time
    • Precise cleavage sites within the transmembrane domain were unresolved
    • In vivo physiological role outside of thyroid was unknown
  4. 2009 High

    The critical in vivo function of CREB3L2 was revealed: it directly activates Sec23a transcription to expand COPII vesicle capacity for secretory cargo export, and its loss causes severe chondrodysplasia due to ER retention of cartilage matrix proteins.

    Evidence Bbf2h7-knockout mouse, promoter-binding and reporter assays, genetic rescue by Sec23a re-expression

    PMID:19767744

    Open questions at the time
    • Whether CREB3L2 regulates additional COPII components beyond Sec23a was unclear
    • Mechanism of CREB3L2 induction in chondrocytes was not determined
  5. 2010 High

    An unbiased genome-wide screen identified the CREB3L2→ATF5→MCL1 anti-apoptotic axis, revealing a survival function beyond vesicular trafficking and connecting CREB3L2 to RAS-MAPK/PI3K oncogenic signaling in glioma.

    Evidence Genome-wide RNAi screen, ChIP, siRNA knockdown, and glioma mouse model

    PMID:20495567

    Open questions at the time
    • Whether the ATF5–MCL1 axis operates in non-malignant secretory cells was untested
    • Direct versus indirect transcriptional activation of ATF5 needed further dissection
  6. 2012 High

    The anti-apoptotic role was confirmed in vivo: CREB3L2 directly activates Atf5 in chondrocytes, whose product drives Mcl1 transcription to prevent ER stress-induced apoptosis during cartilage proliferation; separately, the BBF2H7–Sec23a axis was shown to be required for IGF-I-stimulated procollagen export in dermal fibroblasts, broadening the cell-type scope.

    Evidence Bbf2h7-KO mouse TUNEL assays with ChIP; siRNA knockdown with IGF-I stimulation in fibroblasts

    PMID:22495181 PMID:22936798

    Open questions at the time
    • How IGF-I signaling induces BBF2H7 at the molecular level was incompletely mapped
    • Relative contribution of survival vs. trafficking functions to the KO phenotype was unclear
  7. 2013 High

    A previously unrecognized paracrine signaling function was uncovered: after cleavage, the secreted C-terminal luminal fragment of CREB3L2 directly binds Indian hedgehog and Patched-1, activating Hedgehog signaling and proliferation in neighboring chondrocytes.

    Evidence Co-immunoprecipitation, pull-down, conditioned medium transfer, Hedgehog reporter assay

    PMID:24332809

    Open questions at the time
    • Structural basis of C-terminal fragment interaction with Ihh/Ptch1 was unknown
    • Whether this paracrine mechanism operates in tissues other than cartilage was untested
  8. 2014 High

    The transcriptional regulation of CREB3L2 itself was resolved in chondrocytes: Sox9 directly binds the Bbf2h7 promoter, placing CREB3L2 within the master chondrogenic transcription factor hierarchy.

    Evidence ChIP, promoter-reporter assay with binding-site mutagenesis, Sox9 knockdown

    PMID:24711445

    Open questions at the time
    • Whether other tissue-specific transcription factors regulate CREB3L2 in non-cartilage contexts was unknown
  9. 2017 Medium

    CREB3L2's target gene repertoire was expanded to include Sec24D and a full suite of COPII-enlargement genes (Sec13/31, Tango1, Sedlin, KLHL12), establishing it as a master regulator of large-cargo vesicle biogenesis across vertebrates and cell types including hepatic stellate cells.

    Evidence siRNA knockdown in HSCs with activation assays; medaka loss-of-function with gene expression analysis

    PMID:28500182 PMID:28801610

    Open questions at the time
    • Direct ChIP evidence for all proposed COPII targets in mammalian cells was lacking
    • Medaka findings await confirmation of full conservation in mammals
  10. 2019 High

    Precise S1P/S2P cleavage sites were mapped, and CREB3L2's role as a genome-wide scaling factor for translation was discovered: in pituitary secretory cells, it directly binds ~75% of translation-regulatory gene promoters, downstream of the differentiation factor Tpit.

    Evidence Mass spectrometry and mutagenesis for cleavage-site mapping; ChIP-seq and RNA-seq with Creb3l2-KO pituitary

    PMID:31481663 PMID:31914686

    Open questions at the time
    • Whether translation scaling is a universal function in all CREB3L2-expressing secretory cells was untested
    • Functional significance of amyloid-like BSP aggregates from S2P cleavage products was unclear
  11. 2021 Medium

    Cell-type-specific upstream regulators were identified: androgen receptor directly controls CREB3L2 expression and collaborates with it for ER-to-Golgi trafficking in prostate cancer, while NGF/MAPK/cAMP induces CREB3L2 in neurons where it modulates differentiation via Rab5.

    Evidence ChIP-seq and trafficking assays in prostate cancer cells; OE/KD with pathway inhibitors in PC12 neurons

    PMID:34421533 PMID:34611310

    Open questions at the time
    • Direct transcriptional targets mediating Rab5 regulation were not identified
    • Whether AR–CREB3L2 cooperation is direct at shared promoters was not resolved
  12. 2022 Medium

    Functional redundancy with CREB3L1 was demonstrated: both factors are required for Golgi enlargement and efficient protein secretion during endometrial decidualization, establishing CREB3L2 as part of a broader CREB3-family organelle-remodeling program.

    Evidence siRNA double knockdown with electron microscopy, secretion assay, and transcriptomic time-course in endometrial stromal cells

    PMID:36313580

    Open questions at the time
    • Individual contributions of CREB3L1 vs. CREB3L2 to specific target genes were not separated
    • Whether other CREB3 family members compensate in single-KD conditions was untested
  13. 2023 High

    Post-translational control of CREB3L2 stability and activation was mechanistically dissected in β-cells: glucose-driven O-GlcNAcylation stabilizes full-length CREB3L2 by blocking proteasomal degradation, while mTORC1 promotes its activating cleavage, linking metabolic sensing to COPII-mediated proinsulin export and insulin granule biogenesis.

    Evidence Conditional β-cell Creb3l2-KO mouse, mTORC1/O-GlcNAc inhibitors, live GFP-proinsulin trafficking, glucose tolerance tests

    PMID:38013154

    Open questions at the time
    • Specific O-GlcNAcylation sites on CREB3L2 were not mapped
    • Whether this dual post-translational regulation operates in non-β-cell secretory tissues was unknown
  14. 2025 Medium

    The paracrine Hedgehog function of CREB3L2's C-terminal fragment was extended to tumor immunology: in triple-negative breast cancer, the secreted fragment suppresses CD8+ T cell activation, enabling immune evasion that can be reversed by Hedgehog inhibition; separately, CREB3L2 was found to stabilize SREBP1 via HAT1-mediated acetylation to drive lipogenesis and drug resistance in HCC, and to heterodimerize with ATF4 under proteasome impairment in Aβ42-treated neurons.

    Evidence Tumor-immune co-culture and mouse models; Co-IP and xenograft in HCC; Co-IP and pharmacological manipulation in neurons

    PMID:39792663 PMID:40164587 PMID:41285809

    Open questions at the time
    • Structural basis for C-terminal fragment immunosuppression is unresolved
    • HAT1 acetylation of SREBP1 downstream of CREB3L2 needs independent replication
    • Physiological relevance of CREB3L2–ATF4 heterodimers outside of Aβ pathology is unknown
  15. 2026 High

    The CREB3L2→Sec23a axis was validated in melanocytes, where mild ER stress from tyrosinase synthesis activates BBF2H7 to enhance COPII transport of tyrosinase to melanosomes; loss causes ER retention and hypopigmentation, rescued by either BBF2H7 or Sec23a.

    Evidence Bbf2h7-KO melanocytes with dual genetic rescue, melanin quantification, immunofluorescence

    PMID:41516372

    Open questions at the time
    • Whether other melanogenic enzymes depend on the same pathway is untested
    • Contribution of the C-terminal paracrine fragment in skin biology is unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CREB3L2 interactions with S1P/S2P and with Ihh/Ptch1, the identity of O-GlcNAcylation sites, whether amyloid-like BSP aggregates have signaling or pathological functions, and whether CREB3L2 mutations cause Mendelian skeletal or metabolic disease in humans.
  • No structural model of CREB3L2 or its cleavage intermediates exists
  • Human genetic disease linkage from loss-of-function variants has not been reported
  • Functional significance of S2P-derived amyloid-like peptides is entirely unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 3
Localization
GO:0005634 nucleus 4 GO:0005783 endoplasmic reticulum 3 GO:0005576 extracellular region 2
Pathway
R-HSA-9609507 Protein localization 7 R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 2
Partners
ATF4ATF5HAT1IHHPTCH1SEC23ASOX9SREBF1

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 CREB3L2/BBF2H7 is an ER-resident transmembrane protein with a bZIP domain in the cytoplasmic portion; it is cleaved at the membrane in response to ER stress, and the cleaved N-terminal fragment translocates to the nucleus where it binds directly to CRE sites to activate transcription of target genes. The protein is not expressed under normal conditions but is markedly induced at the translational level during ER stress. Biochemical fractionation, reporter assays, Western blot, siRNA knockdown, overexpression in neuroblastoma cells Molecular and cellular biology High 17178827
2009 BBF2H7/CREB3L2 directly binds a CRE-like sequence in the Sec23a promoter to activate its transcription, promoting COPII-mediated ER-to-Golgi transport of cartilage matrix proteins (type II collagen, COMP). Bbf2h7-knockout mice show severe chondrodysplasia with aggregated matrix proteins in the ER; reintroduction of Sec23a into Bbf2h7−/− chondrocytes fully restores secretion. Bbf2h7-knockout mouse, promoter binding assay (ChIP-like/reporter), rescue experiment with Sec23a transfection, immunofluorescence Nature cell biology High 19767744
2007 Full-length CREB3L2 and FUS/CREB3L2 proteins localize to reticular (ER) cytoplasmic structures, whereas truncated versions lacking the transmembrane domain reside in the nucleus. Transcriptional activation is achieved via box-B, ATF6, and CRE binding sites as well as the GRP78 promoter; the FUS/CREB3L2 chimera shows stronger transcriptional activation than wild-type CREB3L2. Transfection of NIH3T3 and HEK-293 cells with full-length and truncated constructs, reporter assays, subcellular localization imaging Genes, chromosomes & cancer Medium 17117415
2008 Native CREB3L2 is cleaved to a nuclear form by regulated intramembrane proteolysis (S1P and S2P proteases) in normal thyroid cells. Nuclear CREB3L2 stimulates transcription 8-fold from the EVX1 CRE in the absence of cAMP. The CREB3L2–PPARγ fusion protein inhibits transcription from EVX1 6-fold and suppresses thyroglobulin expression in TSH-treated primary thyroid cells. Reporter gene assay (EVX1-CRE), western blot of cleavage products, primary thyroid cell overexpression, co-immunoprecipitation-inferred proteolysis Cancer research High 18757431
2012 BBF2H7/CREB3L2 directly activates transcription of Atf5 in chondrocytes; ATF5 in turn activates Mcl1 transcription to suppress ER stress-induced apoptosis. This BBF2H7–ATF5–MCL1 pathway is specifically required to prevent apoptosis in proliferating chondrocytes, as shown by increased TUNEL staining in Bbf2h7−/− cartilage. Bbf2h7-knockout mouse, TUNEL assay, promoter reporter assay, ChIP, siRNA knockdown The Journal of biological chemistry High 22936798
2013 After ER stress-induced cleavage of BBF2H7/CREB3L2, the luminal C-terminal fragment is secreted into the extracellular space, where it directly binds both Indian hedgehog (Ihh) and its receptor Patched-1, activating Hedgehog signaling in neighboring chondrocytes to stimulate their proliferation. Co-immunoprecipitation, pull-down assay, conditioned medium transfer, Hedgehog reporter assay, chondrocyte proliferation assay Molecular cell High 24332809
2014 Sox9, the master chondrogenesis transcription factor, directly binds the Sox DNA-binding motif in the Bbf2h7 promoter to activate its transcription, placing CREB3L2 downstream of Sox9 in the chondrogenic differentiation program. ChIP assay, promoter reporter assay with Sox9 binding site mutations, Sox9 knockdown in chondrocytes The Journal of biological chemistry High 24711445
2017 CREB3L2 mediates isoform-specific upregulation of the COPII components Sec23A and Sec24D during hepatic stellate cell (HSC) activation. Knockdown of CREB3L2 or Sec23A/Sec24D abrogates HSC activation, demonstrating that CREB3L2-driven ER-to-Golgi trafficking is required for this fibrogenic process. siRNA knockdown, Western blot, immunofluorescence, HSC activation assays Scientific reports Medium 28801610
2017 In medaka fish, BBF2H7 regulates a complete set of COPII vesicle enlargement genes (Sec23/24/13/31, Tango1, Sedlin, KLHL12) essential for accommodating long-chain (type II) collagen for ER-export, providing cargo- and developmental stage-specific UPR transducer function. Genetic loss-of-function in medaka, reporter assays, gene expression analysis; ortholog study The Journal of cell biology Medium 28500182
2019 S1P cleaves BBF2H7 just before its RXXL recognition motif, while S2P cleaves at multiple sites within the transmembrane domain (next to Leu380, Met381, Leu385), generating BBF2H7-derived small peptide (BSP) fragments that aggregate in an amyloid-like manner under ER stress. In vitro protease assay, mass spectrometry of cleavage products, mutagenesis of cleavage sites, cell-based ER stress induction FASEB journal High 31914686
2019 Creb3l2 directly binds ~75% of regulatory and effector genes for translation in pituitary secretory cells, acting as a scaling factor for translation capacity. Its expression is dependent on the pituitary differentiation factor Tpit, placing Creb3l2 downstream of Tpit in the secretory cell differentiation program. ChIP-seq, RNA-seq, Creb3l2 and Tpit knockout mice, ribosome profiling/translation assay Nature communications High 31481663
2010 A genome-wide RNAi screen identified CREB3L2 as a transcriptional activator of ATF5 in malignant glioma, operating downstream of RAS-MAPK or PI3K signaling. CREB3L2 directly activates ATF5 expression, which in turn stimulates MCL1 transcription to promote cell survival. Genome-wide RNAi screen, reporter assay, ChIP, siRNA knockdown, glioma mouse model Nature medicine High 20495567
2012 The BBF2H7-mediated Sec23A pathway is required for IGF-I-induced ER-to-Golgi transport of procollagen in dermal fibroblasts. Both MAPK and PI3K pathways downstream of IGF-I receptor are required for BBF2H7 induction; knockdown of BBF2H7 reduces type I and III collagen expression and causes COPII vehicle hypoplasia and Golgi dysmorphology. siRNA knockdown, immunofluorescence microscopy, Western blot, IGF-I stimulation assays The Journal of investigative dermatology Medium 22495181
2021 CREB3L2 is upregulated by NGF via MAPK and cAMP signaling pathways in PC12 cells; overexpression of CREB3L2 inhibits NGF-induced neurite outgrowth and increases Rab5 GTPase levels, while CREB3L2 depletion enhances morphological differentiation and reduces Rab5 levels, indicating CREB3L2 modulates neuronal differentiation through regulation of Rab5. Overexpression and siRNA knockdown in PC12 cells, immunofluorescence, pathway inhibitors (MAPK, cAMP) Frontiers in molecular neuroscience Medium 34421533
2021 Androgen receptor (AR) directly regulates CREB3L2 expression and collaborates with CREB3L2 to mediate ER-to-Golgi trafficking in prostate cancer cells, controlling androgen-dependent vesicular transport, cell growth, and survival. Single-cell transcriptome analysis, ChIP-seq, siRNA knockdown, ER-to-Golgi trafficking assay Oncogene Medium 34611310
2022 Simultaneous knockdown of CREB3L1 and CREB3L2 in decidualizing endometrial stromal cells impairs Golgi enlargement, causes ER dilation with collagen accumulation, and decreases protein secretion, demonstrating that both factors are required for Golgi remodeling and efficient protein secretion during decidualization. siRNA double knockdown, immunofluorescence, electron microscopy, secretion assay, transcriptomic time-course Frontiers in cell and developmental biology Medium 36313580
2023 Glucose activates CREB3L2 in pancreatic β-cells through two mechanisms: O-GlcNAcylation stabilizes full-length CREB3L2 by impairing its proteasomal degradation, and mTORC1 stimulation enhances its conversion to the transcriptionally active cleavage product (P60). CREB3L2 deletion impairs ER export of proinsulin, prevents formation of nascent insulin secretory granules, and impairs glucose-stimulated insulin secretion in vivo on high-fat diet. Conditional β-cell Creb3l2 KO mouse (Ins1-CreER), inhibitor studies (mTORC1, O-GlcNAc), immunoblot, live GFP-proinsulin trafficking assay, RNAseq, glucose tolerance test Molecular metabolism High 38013154
2025 CREB3L2 overexpression in triple-negative breast cancer leads to its cleavage and secretion of a C-terminal fragment that activates the Hedgehog pathway in neighboring CD8+ T cells, repressing their activation and cytotoxic function, thereby mediating immune evasion. Hedgehog pathway inhibition impedes CREB3L2-overexpressed tumor growth and sensitizes tumors to immune checkpoint blockade. Overexpression and knockdown in tumor cells, co-culture with CD8+ T cells, Hedgehog reporter assay, mouse tumor model, ICB treatment Science advances Medium 39792663
2025 CREB3L2 upregulates SREBP1 protein expression and stability through increased acetylation mediated by histone acetyltransferase-1 (HAT1), driving fatty acid synthesis and contributing to lenvatinib resistance and hepatocellular carcinoma progression. Overexpression and knockdown in HCC cells and xenograft models, Co-IP, acetylation assay, Western blot Cell death & disease Medium 41285809
2025 In neurons exposed to oligomeric Aβ42, CREB3L2 forms heterodimers with ATF4. Proteasome inhibition induced by Aβ42 increases nuclear levels of both CREB3L2 and CREB3L2–ATF4 heterodimers, causing transcriptional dysregulation (e.g., of SNX3). HRI kinase activation decreases CREB3L2 and heterodimer levels, suggesting CREB3L2 is normally kept low by rapid proteasomal degradation. Co-IP for heterodimer detection, proteasome inhibitor treatment, HRI activator treatment, reporter gene assay for target (SNX3), neuronal cell culture Cell death & disease Medium 40164587
2026 BBF2H7/CREB3L2 is activated by mild ER stress induced by abundant tyrosinase synthesis in melanocytes, whereupon it induces Sec23a expression to enhance COPII-mediated anterograde transport of tyrosinase from the ER to melanosomes; loss of BBF2H7 causes tyrosinase accumulation in the ER and reduced melanin production, which is rescued by restoration of BBF2H7 or Sec23a. Bbf2h7-knockout melanocytes, rescue by BBF2H7 or Sec23a re-expression, immunofluorescence, melanin quantification, Western blot International journal of molecular sciences High 41516372

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. Nature cell biology 191 19767744
2010 A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nature medicine 148 20495567
2004 The chimeric FUS/CREB3l2 gene is specific for low-grade fibromyxoid sarcoma. Genes, chromosomes & cancer 145 15139001
2006 BBF2H7, a novel transmembrane bZIP transcription factor, is a new type of endoplasmic reticulum stress transducer. Molecular and cellular biology 135 17178827
2003 Fusion of the FUS and BBF2H7 genes in low grade fibromyxoid sarcoma. Human molecular genetics 121 12915480
2006 Molecular detection of FUS-CREB3L2 fusion transcripts in low-grade fibromyxoid sarcoma using formalin-fixed, paraffin-embedded tissue specimens. The American journal of surgical pathology 87 16931951
2014 Master regulator for chondrogenesis, Sox9, regulates transcriptional activation of the endoplasmic reticulum stress transducer BBF2H7/CREB3L2 in chondrocytes. The Journal of biological chemistry 68 24711445
2008 CREB3L2-PPARgamma fusion mutation identifies a thyroid signaling pathway regulated by intramembrane proteolysis. Cancer research 58 18757431
2013 Chondrocyte proliferation regulated by secreted luminal domain of ER stress transducer BBF2H7/CREB3L2. Molecular cell 53 24332809
2017 UPR transducer BBF2H7 allows export of type II collagen in a cargo- and developmental stage-specific manner. The Journal of cell biology 47 28500182
2007 Characterization of the native CREB3L2 transcription factor and the FUS/CREB3L2 chimera. Genes, chromosomes & cancer 40 17117415
2019 Pituitary cell translation and secretory capacities are enhanced cell autonomously by the transcription factor Creb3l2. Nature communications 36 31481663
2012 The endoplasmic reticulum stress transducer BBF2H7 suppresses apoptosis by activating the ATF5-MCL1 pathway in growth plate cartilage. The Journal of biological chemistry 33 22936798
2017 CREB3L2-mediated expression of Sec23A/Sec24D is involved in hepatic stellate cell activation through ER-Golgi transport. Scientific reports 23 28801610
2010 Fusion of the FUS and CREB3L2 genes in a supernumerary ring chromosome in low-grade fibromyxoid sarcoma. Cancer genetics and cytogenetics 21 20471519
2007 Hyalinizing spindle cell tumor with giant rosettes arising in the lung: report of a case with FUS-CREB3L2 fusion transcripts. Pathology international 20 17295648
2011 The clinical significance of the FUS-CREB3L2 translocation in low-grade fibromyxoid sarcoma. Journal of orthopaedic surgery and research 18 21406083
2014 Deeply located low-grade fibromyxoid sarcoma with FUS-CREB3L2 gene fusion in a 5-year-old boy with review of literature. Diagnostic pathology 14 25183312
2012 BBF2H7-mediated Sec23A pathway is required for endoplasmic reticulum-to-Golgi trafficking in dermal fibroblasts to promote collagen synthesis. The Journal of investigative dermatology 14 22495181
2008 DNA-based polymerase chain reaction for detecting FUS-CREB3L2 in low-grade fibromyxoid sarcoma using formalin-fixed, paraffin-embedded tissue specimens. Diagnostic molecular pathology : the American journal of surgical pathology, part B 13 18382348
2021 CREB3L2 Modulates Nerve Growth Factor-Induced Cell Differentiation. Frontiers in molecular neuroscience 12 34421533
2022 CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells. Frontiers in cell and developmental biology 11 36313580
2021 Single-cell analysis reveals androgen receptor regulates the ER-to-Golgi trafficking pathway with CREB3L2 to drive prostate cancer progression. Oncogene 11 34611310
2021 MicroRNA-92b-3p promotes the progression of liver fibrosis by targeting CREB3L2 through the JAK/STAT signaling pathway. Pathology, research and practice 9 33618248
2015 Promotion of Cancer Cell Proliferation by Cleaved and Secreted Luminal Domains of ER Stress Transducer BBF2H7. PloS one 9 25955804
2021 Mediastinal Low-Grade Fibromyxoid Sarcoma With FUS-CREB3L2 Gene Fusion. Cureus 7 34277226
2025 Noncanonical UPR factor CREB3L2 drives immune evasion of triple-negative breast cancer through Hedgehog pathway modulation in T cells. Science advances 6 39792663
2023 Independent activation of CREB3L2 by glucose fills a regulatory gap in mouse β-cells by co-ordinating insulin biosynthesis with secretory granule formation. Molecular metabolism 6 38013154
2024 Molecular characterization of transcription factor CREB3L2 and CREB3L3 and their role in melanogenesis in Pacific oysters (Crassostrea gigas). Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 5 38604561
2009 Characterization of the human CREB3L2 gene promoter. Oncology reports 4 19212619
2023 CREB3L2 Regulates Hemidesmosome Formation during Epithelial Sealing. Journal of dental research 3 37555472
2019 Production of BBF2H7-derived small peptide fragments via endoplasmic reticulum stress-dependent regulated intramembrane proteolysis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 3 31914686
2022 Low-Grade Fibromyxoid Sarcoma Featuring an Unusual EWSR1-CREB3L2 Gene Fusion: Report of a Rare Case Arising in the Parotid Gland. Avicenna journal of medicine 2 36051504
2014 A case of low-grade fibromyxoid sarcoma with unusual central necrosis in a 77-year-old man confirmed by FUS-CREB3L2 gene fusion. International journal of surgery case reports 2 25437654
2025 Targeting CREB3L2-mediated lipid metabolism overcomes lenvatinib resistance and attenuates the progression of hepatocellular carcinoma. Cell death & disease 1 41285809
2026 Vesicular Transport Mediated by Endoplasmic Reticulum Stress Sensor BBF2H7 Orchestrates Melanin Production During Melanogenesis. International journal of molecular sciences 0 41516372
2026 U2SURP increases CREB3L2 RNA stability and RIOK1 transcription to enhance lenvatinib resistance in hepatocellular carcinoma cells. Pathology, research and practice 0 41997041
2026 PML::RARA-negative APL-mimicking AML with a novel KMT2C::CREB3L2 fusion and RARA/RXRA-mediated sensitivity to all-trans retinoic acid. Annals of hematology 0 41999490
2026 Pi4ka downregulation triggers Creb3l2-dependent lysosomal dysfunction to promote maladaptive tubular remodeling and immune activation in acute kidney injury. Cell death & disease 0 42045152
2025 Modulation of CREB3L2-ATF4 heterodimerization via proteasome inhibition and HRI activation in Alzheimer's disease pathology. Cell death & disease 0 40164587
2025 Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features and CREB3L2::PPARγ Fusion. Head and neck pathology 0 40839045
2020 Toxic effects of endoplasmic reticulum stress transducer BBF2H7-derived small peptide fragments on neuronal cells. Brain research 0 33010207
2010 Characterization of an alternative transcript of the human CREB3L2 gene. Oncology reports 0 20878102