Affinage

CREB3L1

Cyclic AMP-responsive element-binding protein 3-like protein 1 · UniProt Q96BA8

Length
519 aa
Mass
57.0 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CREB3L1 (OASIS) is an ER-resident, membrane-bound bZIP transcription factor that couples diverse extracellular signals to cell-type-specific transcriptional programs governing secretory capacity, differentiation, cell-cycle control, and extracellular matrix production. Under basal conditions, CREB3L1 is held in check by HRD1-mediated ubiquitin–proteasome degradation; ER stress, ceramide, BMP2, TGF-β, or viral infection triggers its regulated intramembrane proteolysis by Golgi-resident S1P/S2P, releasing an N-terminal fragment that translocates to the nucleus (facilitated by KPNA2) and activates target genes including Col1a1, p21, VEGFA, SEC23A, SEC24D, Pcsk1, and C6ST1, often in cooperation with Smad4 or HIF-1α (PMID:15665855, PMID:16417584, PMID:22705851, PMID:25310401, PMID:26558437, PMID:36192735). CREB3L1 knockout mice exhibit severe osteopenia from deficient type I collagen, impaired astrocyte and goblet cell differentiation, and prolonged gliosis after brain injury, while CREB3L1 also arrests the cell cycle at G2/M via p53-independent p21 induction after DNA damage or viral infection (PMID:19767743, PMID:22262831, PMID:21767813, PMID:37178686). Loss-of-function mutations in the bZIP domain cause osteogenesis imperfecta through failure to activate COPII component genes SEC23A and SEC24D (PMID:28817112, PMID:30657919).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 Medium

    Identifying CREB3L1 as a new CREB/ATF family member expressed in astrocytes established its tissue context and set the stage for functional dissection of a previously unknown ER-associated transcription factor.

    Evidence Differential display screening and in situ hybridization in mouse CNS after cryo-injury

    PMID:10350641

    Open questions at the time
    • No function assigned beyond expression pattern
    • Protein product not characterized biochemically
    • No target genes identified
  2. 2002 Medium

    Domain dissection revealed that CREB3L1 is an ER-anchored transcription factor whose C-terminal transmembrane domain restricts it from the nucleus, establishing the principle that proteolytic release would be required for transcriptional activation.

    Evidence Deletion constructs, reporter assays, and subcellular localization in transfected cells

    PMID:12054625 PMID:12480185

    Open questions at the time
    • Protease(s) responsible for cleavage not identified
    • Physiological triggers for activation unknown
    • Endogenous target genes not determined
  3. 2005 High

    Demonstrating that ER stress triggers regulated intramembrane proteolysis of CREB3L1 to release a nuclear-translocating N-terminal fragment that induces BiP and protects astrocytes from ER-stress-induced death established CREB3L1 as a bona fide ER stress transducer, paralleling ATF6.

    Evidence Knockdown and overexpression in astrocytes, nuclear fractionation, BiP induction, and cell death assays

    PMID:15665855

    Open questions at the time
    • Identity of the cleaving proteases not yet confirmed
    • Spectrum of target genes beyond BiP unknown
    • In vivo physiological relevance not tested
  4. 2006 High

    Identifying S1P and S2P as the Golgi-resident proteases responsible for CREB3L1 cleavage resolved the enzymatic basis of its activation and placed it within the same RIP pathway as ATF6 and SREBP.

    Evidence S1P/S2P mutant cell lines, protease inhibitors, and deletion mutant analysis

    PMID:16417584

    Open questions at the time
    • Mechanism of CREB3L1 translocation from ER to Golgi unclear (no canonical Golgi localization signal)
    • Regulation of S1P/S2P access to CREB3L1 not defined
  5. 2009 High

    The OASIS knockout mouse revealed that CREB3L1 is essential for bone formation by directly activating Col1a1 transcription in osteoblasts, providing the first in vivo loss-of-function phenotype and identifying a key target gene.

    Evidence OASIS−/− mouse with severe osteopenia, ChIP on Col1a1 promoter, BMP2 stimulation experiments

    PMID:19767743

    Open questions at the time
    • Whether the osteopenia phenotype is solely Col1a1-dependent or involves additional targets not resolved
    • Mechanism linking BMP2 to OASIS RIP not elucidated
  6. 2010 High

    Osteoblast-specific rescue of OASIS−/− mice normalized bone collagen but not growth retardation, revealing that CREB3L1 has both cell-autonomous (osteoblast) and systemic (GH/IGF-1 axis) roles in skeletal physiology.

    Evidence Transgenic rescue under Col1a1 promoter, histology, serum GH/IGF-1 ELISA

    PMID:21047569

    Open questions at the time
    • Tissue(s) responsible for the GH/IGF-1 deficiency not identified
    • Direct versus indirect regulation of GH axis by CREB3L1 unclear
  7. 2011 High

    Demonstrating that diverse viruses trigger CREB3L1 cleavage to induce p21 and block proliferation of infected cells established a novel antiviral function via cell-cycle arrest, independent of the classical UPR.

    Evidence Infection with γ-HV68, HCV, WNV, Sendai virus; CREB3L1 knockdown/overexpression; proliferation assays

    PMID:21767813

    Open questions at the time
    • Viral mechanism triggering CREB3L1 cleavage not defined
    • Whether viruses actively silence CREB3L1 transcription or select for low-expressing cells unclear
  8. 2012 High

    Multiple studies converged to show that CREB3L1 drives cell-type-specific differentiation programs: goblet cell maturation in the intestine and astrocyte differentiation from neural precursors (via Gcm1 induction and GFAP promoter demethylation), while HRD1-mediated ubiquitination was identified as the basal degradation mechanism keeping CREB3L1 inactive.

    Evidence OASIS−/− mice (goblet cell and astrocyte phenotypes), Gcm1 rescue of NPC differentiation, Co-IP of HRD1-OASIS, ubiquitination assays in Hrd1−/− cells

    PMID:22262831 PMID:22705851 PMID:22828627

    Open questions at the time
    • How ER stress dissociates HRD1-OASIS interaction mechanistically not defined
    • Gcm1 as the sole mediator of astrocyte differentiation downstream of OASIS not confirmed
  9. 2012 High

    Linking doxorubicin-induced ceramide synthesis to S1P/S2P-mediated CREB3L1 cleavage and p21-dependent growth arrest provided a mechanistic explanation for how this chemotherapeutic agent engages a non-canonical cell-cycle checkpoint.

    Evidence Ceramide synthesis and S1P/S2P inhibitors, siRNA knockdown, overexpression, proliferation assays

    PMID:23256041

    Open questions at the time
    • How ceramide promotes CREB3L1 transit from ER to Golgi not determined
    • Relevance in clinical doxorubicin resistance not tested in patient samples
  10. 2013 High

    Genome-wide target identification (ChIP-on-chip) in metastatic breast cancer showed that CREB3L1 directly represses angiogenesis-related genes and suppresses metastasis in vivo, while in retinal epithelial cells it directly activates VEGFA, highlighting profound cell-type specificity of its transcriptional outputs.

    Evidence ChIP-on-chip in breast cancer cells, in vivo mammary tumor regression, ChIP on VEGFA promoter in ARPE-19 cells

    PMID:23383089 PMID:24126059

    Open questions at the time
    • Mechanism determining activator versus repressor function at different loci not resolved
    • Cofactors distinguishing pro- versus anti-angiogenic programs not identified
  11. 2014 High

    Identifying TGF-β as an activator of CREB3L1 RIP (via TM4SF20 suppression) and Smad4 as a nuclear co-activator partner connected CREB3L1 to a major fibrotic signaling axis and explained sustained collagen synthesis beyond canonical Smad-mediated transcription.

    Evidence TGF-β treatment, TM4SF20 knockdown/overexpression, Co-IP of CREB3L1-N with Smad4, reporter assays

    PMID:25310401

    Open questions at the time
    • How TM4SF20 mechanistically inhibits CREB3L1 RIP not elucidated
    • Whether Smad4 interaction is direct or bridged not resolved structurally
  12. 2015 High

    Physical interaction of CREB3L1 with HIF-1α through the bZIP domain and cooperative activation of HRE-driven genes including VEGFA in bone revealed that CREB3L1 integrates ER stress and hypoxia signaling to regulate vascularization.

    Evidence Co-immunoprecipitation, HRE-luciferase reporter, OASIS−/− mouse metatarsal angiogenesis assay

    PMID:26558437

    Open questions at the time
    • Structural basis of CREB3L1–HIF-1α interaction unknown
    • Whether this interaction occurs genome-wide or only at select loci not determined
  13. 2017 Medium

    Human genetics linked CREB3L1 loss-of-function mutations to osteogenesis imperfecta, with the pathogenic mechanism traced to failure of CREB3L1 to activate COPII components SEC23A and SEC24D, connecting transcriptional control of secretory pathway genes to collagen export and bone disease.

    Evidence Exome sequencing in consanguineous OI family, luciferase assay of bZIP-domain mutant, SEC24D protein reduction

    PMID:28817112 PMID:30657919

    Open questions at the time
    • Limited number of OI families reported
    • Whether SEC23A/SEC24D reduction fully explains the OI phenotype versus additional CREB3L1 targets not tested
    • No animal model recapitulating the specific human mutation
  14. 2017 High

    Placing CREB3L1 downstream of PERK in mesenchymal triple-negative breast cancer as a pro-metastatic effector showed that CREB3L1's role in cancer is context-dependent—tumor-suppressive in some settings but pro-invasive when activated by the PERK–UPR axis.

    Evidence PERK inhibitor and CREB3L1 knockdown/overexpression, invasion assays, in vivo metastasis models

    PMID:29057869

    Open questions at the time
    • How PERK activates CREB3L1 (direct phosphorylation, transcriptional, or RIP-mediated) not resolved
    • Determinants of tumor-suppressive versus pro-metastatic CREB3L1 function not identified
  15. 2021 Medium

    Discovery that full-length (uncleaved) CREB3L1 accumulates at damaged nuclear envelope sites and suppresses DNA damage revealed a RIP-independent structural role at the nuclear envelope, expanding CREB3L1 function beyond transcription.

    Evidence Live imaging, co-localization with LINC complex and NE repair factors (BAF, ESCRT-III), DNA damage assays under NE stress

    PMID:34226518

    Open questions at the time
    • Mechanism by which full-length CREB3L1 is recruited to NE damage sites unknown
    • Whether NE function is independent of or coordinated with ER stress sensing not established
    • Single study without independent replication
  16. 2023 High

    Establishing that CREB3L1 arrests astrocytes and osteoblasts at G2/M via p53-independent p21 induction after DNA damage, and that epigenomic reactivation of silenced CREB3L1 suppresses glioblastoma, unified the tumor-suppressive and differentiation functions under a common cell-cycle control mechanism.

    Evidence OASIS−/− mice with brain injury, ChIP for p21 promoter, flow cytometry, epigenomic CREB3L1 promoter demethylation in glioblastoma xenografts

    PMID:37178686

    Open questions at the time
    • Mechanism of p53-independent p21 activation by CREB3L1 at the chromatin level not defined
    • Whether G2/M arrest is universal across all CREB3L1-expressing cell types not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the structural basis for CREB3L1's cell-type-specific target gene selection; (2) the mechanism by which CREB3L1 translocates from ER to Golgi for S1P/S2P cleavage in the absence of a canonical Golgi localization signal; (3) how full-length CREB3L1 functions at damaged nuclear envelopes independently of RIP; and (4) the determinants that switch CREB3L1 between tumor-suppressive and pro-metastatic roles in different cancer contexts.
  • No structural model of CREB3L1 or its complexes with Smad4/HIF-1α
  • ER-to-Golgi transport mechanism unresolved
  • Nuclear envelope function independently replicated only once
  • Context-dependent oncogene versus tumor suppressor switch not mechanistically explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 5
Localization
GO:0005634 nucleus 6 GO:0005783 endoplasmic reticulum 4 GO:0005794 Golgi apparatus 2 GO:0005635 nuclear envelope 1
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1266738 Developmental Biology 4 R-HSA-1474244 Extracellular matrix organization 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-9609507 Protein localization 3
Partners
HIF1AHRD1KPNA2NESPRIN2SMAD4SUN2TM4SF20

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CREB3L1 (OASIS) was identified as a novel member of the CREB/ATF family of transcription factors, expressed in long-term cultured astrocytes and gliotic tissue, with a putative role in gliotic events based on its induction after cryo-injury of the mouse cerebral cortex. Differential display screening, in situ hybridization, expression analysis in mouse embryo and injured CNS Brain research. Molecular brain research Medium 10350641
2002 OASIS/CREB3L1 is a transcriptional activator that activates transcription through box-B elements (but not somatostatin CRE); its C-terminal transmembrane domain anchors it to the ER and represses transcriptional activity, while truncation of the transmembrane domain relocates it to the nucleus and markedly increases transcriptional activity. Luciferase reporter assays, western blot, subcellular localization by transfection and deletion constructs Biochemical and biophysical research communications Medium 12054625
2002 OASIS/CREB3L1 binds CRE sequences (shown by gel shift assay), has a strong N-terminal transcriptional activation domain rich in acidic amino acids, and contains a C-terminal repression domain not previously described in CREB/ATF members. Gel shift assay, GAL4-UAS-luciferase reporter assay, deletion construct analysis in COS7 cells Brain research. Molecular brain research Medium 12480185
2005 OASIS/CREB3L1 is an ER stress transducer: it is a membrane-bound bZIP transcription factor that is cleaved at the membrane in response to ER stress (regulated intramembrane proteolysis), and the released N-terminal cytoplasmic domain translocates to the nucleus where it activates transcription of target genes via ER stress-responsive and cAMP-responsive elements. Overexpression induced BiP and suppressed ER-stress-induced cell death; knockdown reduced BiP and increased susceptibility to ER stress in astrocytes. Knockdown and overexpression in astrocytes, reporter assays, western blot, nuclear fractionation, BiP induction assay Nature cell biology High 15665855
2005 A novel FUS/CREB3L1 fusion gene was identified in a case of low-grade fibromyxoid sarcoma (LGFMS), where the N-terminal domain of FUS is fused in-frame to CREB3L1 (analogous to the more common FUS/CREB3L2 fusion), establishing CREB3L1 rearrangement as an alternative oncogenic driver in LGFMS. RT-PCR, sequencing, histopathologic analysis across multiple centers Laboratory investigation High 15640831
2006 OASIS/CREB3L1 is processed by Site-1 Protease (S1P) and Site-2 Protease (S2P) — the same Golgi-resident proteases that cleave ATF6 — in response to ER stress, and its cleavage requires translocation to the Golgi apparatus. Unlike ATF6, OASIS does not have a significant luminal Golgi localization signal, suggesting alternative mechanisms for its Golgi translocation. Protease inhibitor studies, S1P/S2P mutant cell lines, deletion mutant analysis, subcellular fractionation Journal of neurochemistry High 16417584
2008 OASIS/CREB3L1 directly binds a CRE site in the GCMa/Gcm1 promoter and stimulates GCMa transcription in trophoblast cells; knockdown of OASIS in BeWo cells decreased endogenous GCMa mRNA. Overexpression of OASIS in choriocarcinoma cells led to placental cell fusion. Promoter mapping, reporter assays, siRNA knockdown, gel shift/ChIP, overexpression in trophoblast cell lines Nucleic acids research Medium 18495750
2009 OASIS/CREB3L1 is required for bone formation: it activates transcription of Col1a1 (type I collagen) through a UPRE-like sequence in the osteoblast-specific Col1a1 promoter. OASIS-/- mice show severe osteopenia with decreased type I collagen in the bone matrix and dilated rough ER in osteoblasts. BMP2 induces OASIS expression and accelerates its regulated intramembrane proteolysis. OASIS-/- mouse model, ChIP, reporter assay, histological analysis, BMP2 stimulation experiments Nature cell biology High 19767743
2010 In pancreatic beta-cells, active nuclear OASIS/CREB3L1 upregulates genes involved in extracellular matrix production and protein transport (but not classical UPR genes like BiP/GRP78), demonstrating that the repertoire of OASIS target genes is cell-type dependent. Endogenous OASIS is regulated post-transcriptionally by miR-140 in beta-cells. Microarray after inducible nuclear OASIS expression in INS-1 cells, reporter assay, miRNA analysis Endocrinology Medium 20668028
2010 Osteoblast-specific re-expression of OASIS in OASIS-/- mice rescues osteopenia and normalizes type I collagen mRNA levels and rough ER morphology, but does not rescue growth retardation, which is attributed to reduced serum GH and IGF-1 levels — demonstrating distinct osteoblast-dependent and -independent skeletal mechanisms. Transgenic rescue experiment (osteoblast-specific Col1a1 promoter), histology, RT-PCR, ELISA for GH/IGF-1 Bone High 21047569
2011 CREB3L1/OASIS is proteolytically cleaved upon infection with diverse DNA and RNA viruses (murine γ-herpesvirus 68, HCV, West Nile virus, Sendai virus), allowing its N-terminus to enter the nucleus and induce cell-cycle inhibitors (including p21) to block proliferation of virus-infected cells. CREB3L1 expression is silenced in proliferating cells harboring HCV or WNV replicons. Viral infection models, western blot for CREB3L1 cleavage, gene expression analysis, knockdown/overexpression, proliferation assays Cell host & microbe High 21767813
2011 EWSR1-CREB3L1 fusion transcript was identified in small cell osteosarcoma; the chimeric protein (~70 kDa) shows nuclear localization (confirmed by immunohistochemistry) rather than the normal perinuclear localization of wild-type CREB3L1, consistent with function as a constitutively active nuclear transcriptional regulator. RACE, RT-PCR, sequencing, genomic breakpoint confirmation, immunohistochemistry, western blot Genes, chromosomes & cancer Medium 21987447
2012 OASIS/CREB3L1 promotes terminal differentiation of goblet cells in the large intestine: OASIS-/- mice show reduced goblet cell numbers, decreased mucus production, abnormal mucous vesicle and rough ER morphology, decreased mature goblet cell markers, and increased early goblet cell markers. OASIS is activated by mild ER stress during goblet cell differentiation. OASIS-/- mouse model, morphological analysis, in vitro knockdown in goblet cell culture model, marker expression analysis The Journal of biological chemistry High 22262831
2012 HRD1, an ER-resident E3 ubiquitin ligase, ubiquitinates and destabilizes OASIS/CREB3L1 under normal conditions via the ubiquitin-proteasome pathway. ER stress dissociates the HRD1-OASIS interaction, stabilizing OASIS and enabling its transcriptional activity. Stabilization of OASIS in Hrd1-/- cells enhances collagen fiber production during osteoblast differentiation. Co-immunoprecipitation, HRD1 knockout cells, ubiquitination assay, proteasome inhibitor studies, collagen production assay Cell death and differentiation High 22705851
2012 OASIS/CREB3L1 is required for astrocyte differentiation from neural precursor cells: OASIS-/- mouse cortices contain fewer astrocytes and more neural precursor cells during embryonic development. OASIS directly induces Gcm1 transcription (a target required for astrocyte differentiation in Drosophila), and Gcm1 introduction into OASIS-/- NPCs rescues differentiation by accelerating Gfap promoter demethylation. OASIS-/- mouse model, primary NPC culture, Gcm1 rescue experiment, GFAP promoter methylation analysis Nature communications High 22828627
2012 Doxorubicin stimulates de novo ceramide synthesis, which activates CREB3L1 by stimulating its proteolytic cleavage by Site-1 Protease and Site-2 Protease. The released N-terminal domain enters the nucleus and activates transcription of cell-cycle inhibitors including p21. Knockdown of CREB3L1 confers doxorubicin resistance; overexpression enhances sensitivity. Ceramide synthesis inhibitors, S1P/S2P inhibitor studies, siRNA knockdown, overexpression, cell proliferation assays, nuclear fractionation eLife High 23256041
2013 EWSR1-CREB3L1 fusion transcripts were identified as the predominant genetic event in pure sclerosing epithelioid fibrosarcoma (SEF) by RT-PCR and mRNA sequencing, distinct from FUS-CREB3L2 fusions in LGFMS, supporting these as different tumor types with different molecular drivers. FISH, RT-PCR, mRNA sequencing in 10 primary SEF tumors The American journal of surgical pathology Medium 24441665
2013 CREB3L1 suppresses metastasis in breast cancer: reintroduction of CREB3L1 into metastatic cells reduced invasion and migration in vitro, and in vivo led to regression of primary tumors in 70% of animals via impaired angiogenesis. ChIP-on-chip identified direct CREB3L1 target genes, including genes involved in angiogenesis that are repressed by CREB3L1. Transfection of metastatic cells, in vitro invasion/migration assays, in vivo rat mammary tumor model, microarray, ChIP-on-chip Molecular and cellular biology High 24126059
2013 In human glioma cell lines, OASIS/CREB3L1 knockdown attenuates the UPR (reduced BiP/GRP78 and GRP94 induction), decreases chondroitin sulfate proteoglycan extracellular matrix proteins, and reduces cell migration. OASIS protein in glioma cells is N-glycosylated at Asn-513. siRNA knockdown, western blot, ER stress induction, migration assays, glycosylation analysis PloS one Medium 23335989
2013 EWSR1-CREB3L1 fusion was found as an alternative molecular aberration in LGFMS, confirmed by DNA sequencing of RT-PCR products and FISH, expanding the genetic spectrum of LGFMS. RT-PCR, DNA sequencing, FISH The American journal of surgical pathology Medium 23588368
2013 CREB3L1 regulates VEGFA transcription in human retinal pigment epithelial cells (ARPE-19): OASIS directly binds a CRE-like site at ~-500 bp of the VEGFA promoter (confirmed by ChIP), and is the most effective UPR transcription factor driving VEGFA promoter activity after ER stress in these cells. Reporter assays with VEGFA promoter deletion/mutation constructs, ChIP, ER stress induction, comparison of ATF6/XBP1/ATF4/OASIS PloS one Medium 23383089
2014 TGF-β induces proteolytic activation of CREB3L1 through inhibition of TM4SF20 (which normally inhibits RIP of CREB3L1). The released N-terminal domain enters the nucleus and binds Smad4 to activate transcription of genes encoding collagen assembly extracellular matrix proteins, providing a mechanism for sustained TGF-β-induced collagen synthesis. TGF-β treatment of A549 cells, TM4SF20 knockdown/overexpression, Co-IP of CREB3L1 N-terminal domain with Smad4, reporter assay, western blot for RIP PloS one High 25310401
2014 OASIS/CREB3L1 is epigenetically silenced by promoter hypermethylation in bladder cancer, and re-expression suppresses tumor cell migration and colony growth. HTRA3 was identified as a putative target gene of CREB3L1 in invasive bladder cancer cells. Pyrosequencing of CpG methylation, siRNA re-expression, migration assay, colony assay, target gene identification Epigenetics Medium 25625847
2015 OASIS/CREB3L1 modulates the hypoxia signaling pathway by physically interacting with HIF-1α through its bZIP domain (shown by co-immunoprecipitation), and the OASIS-N fragment promotes transcription of HIF-1α target genes (including VEGFA) via hypoxia-response elements. OASIS-deficient mice show decreased VEGFA expression and retarded vascularization in bone tissue. Co-immunoprecipitation, luciferase reporter assay with HRE, RT-PCR, immunostaining, metatarsal angiogenesis assay in OASIS-/- mice Scientific reports High 26558437
2015 CREB3L1 is a transcriptional regulator of the arginine vasopressin (AVP) gene in rat hypothalamus; cAMP (via forskolin) upregulates Creb3l1 mRNA and protein and increases Avp promoter activity, an effect blunted by Creb3l1 shRNA. Glucocorticoids (dexamethasone) negatively regulate Creb3l1 expression, thereby reducing AVP induction. shRNA knockdown of Creb3l1 in AtT20 cells and hypothalamic organotypic cultures, AVP promoter reporter assay, in vivo dexamethasone injection Molecular brain Medium 26503226
2015 In the osmotically challenged rat hypothalamus, CREB3L1 acts as a transcriptional mediator of the ER stress response: dominant-negative CREB3L1 introduced into the SON by lentiviral vector decreased Chop and unspliced Xbp1 mRNA levels, but not BiP or Atf4. Lentiviral delivery of dominant-negative CREB3L1 into rat SON, RT-PCR for ER stress markers PloS one Medium 25915053
2017 CREB3L1 acts downstream of PERK kinase specifically in mesenchymal subtype triple-negative breast cancer to mediate pro-metastatic functions: genetic or pharmacological inhibition of CREB3L1 suppresses cancer cell invasion and metastasis, placing CREB3L1 as a key effector of PERK-driven invasion. PERK inhibitor treatment, CREB3L1 knockdown/overexpression, invasion assays, in vivo metastasis models Nature communications High 29057869
2017 A pathogenic missense variant p.(Ala304Val) in the bZIP domain of CREB3L1 reduces its DNA-binding ability (shown by luciferase assay) and decreases transcription of SEC23A and SEC24D (COPII components), and reduces SEC24D protein levels, demonstrating a functional link between OASIS and the COPII secretory complex in OI pathogenesis. In vitro structural modeling, luciferase transcriptional activity assay, overexpression of mutant OASIS, western blot for SEC24D Human molecular genetics Medium 30657919
2017 CREB3L1 (OASIS) disruption of a DNA-binding site in the bZIP domain prevents activation of SEC24D transcription in human OI; in a consanguineous family with a CREB3L1 variant causing OI, OASIS fails to act on transcriptional targets including SEC24D (a COPII coat component), linking defective OASIS signaling to impaired secretory pathway function. Exome sequencing, functional validation by reporter assay, identification of SEC24D as target Genetics in medicine Medium 28817112
2017 CREB3L1 regulates secretory pathway capacity in thyroid cells: TSH stimulation upregulates CREB3L1, which increases expression of ER-Golgi transport factors and causes Golgi complex expansion; dominant-negative CREB3L1 impairs TSH-induced Golgi expansion, establishing CREB3L1 as a downstream effector coupling cargo load to secretory pathway capacity. TSH stimulation of thyroid cells, dominant-negative CREB3L1 construct, Golgi volume quantification, transport factor mRNA analysis Journal of cell science Medium 29093023
2017 Orphan nuclear receptor Nr4a1 directly activates Creb3l1 transcription by binding a single NBRE site in the Creb3l1 promoter, as a downstream effector of cAMP signaling; shRNA silencing of Nr4a1 in AtT20 cells prevents cAMP-induced Creb3l1 upregulation. CpG methylation of the Creb3l1 proximal promoter determines accessibility of this pathway. shRNA silencing of Nr4a1, promoter reporter assay with NBRE site mutations, microarray mining, bisulfite methylation analysis Frontiers in molecular neuroscience Medium 29311806
2020 CREB3L1 directly regulates transcription of Pcsk1 (encoding prohormone convertase PC1/3) by binding a G-box motif in the Pcsk1 promoter in endocrine cells; overexpression of Creb3l1 in the supraoptic nucleus increases Pcsk1, while knockdown decreases it, establishing CREB3L1 as a regulator of the neuropeptide processing enzyme supply chain. RNA-seq after Creb3l1 knockdown in AtT20 cells, in vitro promoter activity assay, direct binding studies, viral overexpression/knockdown in rat supraoptic nucleus Journal of neuroendocrinology Medium 32319174
2021 OASIS/CREB3L1 accumulates as a full-length form (not cleaved) at sites of damaged nuclear envelope (NE) where lamins are depleted, colocalizes with LINC complex components SUN2 and Nesprin-2, and with NE repair factors (BAF, LEM domain proteins, ESCRT-III component). OASIS suppresses DNA damage and restores nuclear shape under NE stress, revealing a novel NE stress response function distinct from its ER stress/RIP function. Live imaging, immunofluorescence, co-localization with NE repair factors, DNA damage assays, nuclear deformation assays under NE stress Cell death discovery Medium 34226518
2022 In anaplastic thyroid carcinoma (ATC), CREB3L1 promotes invasion and metastasis by activating ECM signaling (collagen subtypes), and mediates activation of α-SMA-positive cancer-associated fibroblasts (CAFs) through IL-1α production; KPNA2 mediates nuclear translocation of CREB3L1, linking it to downstream ECM gene activation. CREB3L1 knockdown/overexpression in ATC cells, zebrafish and nude mouse xenograft models, cytokine array screening, single-cell RNA-seq, CAF co-culture assays Molecular cancer Medium 36192735
2023 OASIS/CREB3L1 arrests the cell cycle at G2/M phase after DNA damage by directly inducing p21 transcription, independent of p53. This cell-cycle arrest function is dominant in astrocytes and osteoblasts. In a brain injury model, OASIS-/- reactive astrocytes show sustained proliferation and prolonged gliosis. Epigenomic removal of CREB3L1 promoter hypermethylation in glioblastoma xenografts suppresses tumorigenesis. OASIS-/- mice, DNA damage assays, flow cytometry for cell cycle, ChIP for p21 promoter, brain injury model, epigenomic engineering in glioblastoma xenografts Cell reports High 37178686
2023 C5a-C5aR1 activates ER stress via the PERK-eIF2α-ATF4 pathway, with CREB3L1 acting as a key downstream mediator that promotes vascular smooth muscle cell osteogenic transdifferentiation and vascular calcification by inducing COL1α1 expression. VSMC calcification model, C5aR1 antagonist (PMX53), in vivo chronic kidney disease mouse model, pathway inhibition studies, calcium deposition/osteogenic marker assays Cardiovascular research Medium 37603848
2014 OASIS/CREB3L1 regulates chondroitin 6-O-sulfotransferase 1 (C6ST1) gene transcription in reactive astrocytes: OASIS knockout mice show attenuated CS-C immunoreactivity after brain stab injury, C6ST1 mRNA/protein induction is lost in OASIS-/- injured cortices, and a C-terminal deletion OASIS mutant directly activates C6ST1 transcription through the first intron region, promoting CSPG sulfation and creating a non-permissive environment for axonal regeneration. OASIS-/- mouse brain stab injury model, RT-PCR, immunostaining, C6ST1 reporter driven by intron 1, neurite outgrowth assays on membrane fractions Journal of neurochemistry Medium 24716865

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation. Nature cell biology 293 19767743
2005 OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes. Nature cell biology 247 15665855
2014 Higher disease activity leads to more structural damage in the spine in ankylosing spondylitis: 12-year longitudinal data from the OASIS cohort. Annals of the rheumatic diseases 243 24812292
2005 Clinicopathologic and molecular genetic characterization of low-grade fibromyxoid sarcoma, and cloning of a novel FUS/CREB3L1 fusion gene. Laboratory investigation; a journal of technical methods and pathology 218 15640831
2012 The 8q24 gene desert: an oasis of non-coding transcriptional activity. Frontiers in genetics 126 22558003
2006 Cleavage of the membrane-bound transcription factor OASIS in response to endoplasmic reticulum stress. Journal of neurochemistry 122 16417584
2017 Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1. Nature communications 115 29057869
2014 Recurrent EWSR1-CREB3L1 gene fusions in sclerosing epithelioid fibrosarcoma. The American journal of surgical pathology 115 24441665
2012 Doxorubicin blocks proliferation of cancer cells through proteolytic activation of CREB3L1. eLife 112 23256041
2013 EWSR1-CREB3L1 gene fusion: a novel alternative molecular aberration of low-grade fibromyxoid sarcoma. The American journal of surgical pathology 101 23588368
2013 Deficiency for the ER-stress transducer OASIS causes severe recessive osteogenesis imperfecta in humans. Orphanet journal of rare diseases 96 24079343
1999 Identification of a novel gene, OASIS, which encodes for a putative CREB/ATF family transcription factor in the long-term cultured astrocytes and gliotic tissue. Brain research. Molecular brain research 96 10350641
2006 An endangered oasis of aquatic microbial biodiversity in the Chihuahuan desert. Proceedings of the National Academy of Sciences of the United States of America 92 16618921
2000 The Santa Barbara Basin is a symbiosis oasis. Nature 92 10638755
2022 CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment. Molecular cancer 90 36192735
2021 Long-term Safety and Efficacy of Etrasimod for Ulcerative Colitis: Results from the Open-label Extension of the OASIS Study. Journal of Crohn's & colitis 88 33475734
1989 Isolation and identification of Pseudomonas spp. from Schirmacher Oasis, Antarctica. Applied and environmental microbiology 80 2930174
2011 A microbial oasis in the hypersaline Atacama subsurface discovered by a life detector chip: implications for the search for life on Mars. Astrobiology 76 22149750
2012 Unfolded protein response, activated by OASIS family transcription factors, promotes astrocyte differentiation. Nature communications 72 22828627
2011 The membrane-bound transcription factor CREB3L1 is activated in response to virus infection to inhibit proliferation of virus-infected cells. Cell host & microbe 72 21767813
2002 OASIS is a transcriptional activator of CREB/ATF family with a transmembrane domain. Biochemical and biophysical research communications 72 12054625
2011 Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors. IUBMB life 69 21438114
2024 Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA 63 39172446
2012 The endoplasmic reticulum stress transducer OASIS is involved in the terminal differentiation of goblet cells in the large intestine. The Journal of biological chemistry 58 22262831
2019 Circulating DNAs, a Marker of Neutrophil Extracellular Traposis and Cancer-Related Stroke: The OASIS-Cancer Study. Stroke 57 31394991
2018 Oasis 2: improved online analysis of small RNA-seq data. BMC bioinformatics 55 29444641
2017 Monoallelic and biallelic CREB3L1 variant causes mild and severe osteogenesis imperfecta, respectively. Genetics in medicine : official journal of the American College of Medical Genetics 54 28817112
2016 Cancer Cell-Derived Extracellular Vesicles Are Associated with Coagulopathy Causing Ischemic Stroke via Tissue Factor-Independent Way: The OASIS-CANCER Study. PloS one 54 27427978
2013 CREB3L1 is a metastasis suppressor that represses expression of genes regulating metastasis, invasion, and angiogenesis. Molecular and cellular biology 53 24126059
2014 Sustained induction of collagen synthesis by TGF-β requires regulated intramembrane proteolysis of CREB3L1. PloS one 52 25310401
2004 Bacterial diversity of a soil sample from Schirmacher Oasis, Antarctica. Cellular and molecular biology (Noisy-le-Grand, France) 48 15559969
2012 Activation of OASIS family, ER stress transducers, is dependent on its stabilization. Cell death and differentiation 47 22705851
2009 An orthogonal active site identification system (OASIS) for proteomic profiling of natural product biosynthesis. ACS chemical biology 47 19785476
2015 Oasis: online analysis of small RNA deep sequencing data. Bioinformatics (Oxford, England) 46 25701573
2010 OASIS/CREB3L1 induces expression of genes involved in extracellular matrix production but not classical endoplasmic reticulum stress response genes in pancreatic beta-cells. Endocrinology 45 20668028
2001 Expression of the novel transcription factor OASIS, which belongs to the CREB/ATF family, in mouse embryo with special reference to bone development. Histochemistry and cell biology 43 11685542
2017 High diversity and suggested endemicity of culturable Actinobacteria in an extremely oligotrophic desert oasis. PeerJ 42 28480140
2013 OASIS/CREB3L1 is induced by endoplasmic reticulum stress in human glioma cell lines and contributes to the unfolded protein response, extracellular matrix production and cell migration. PloS one 36 23335989
2011 A novel EWSR1-CREB3L1 fusion transcript in a case of small cell osteosarcoma. Genes, chromosomes & cancer 36 21987447
2015 Primary renal sclerosing epithelioid fibrosarcoma: report of 2 cases with EWSR1-CREB3L1 gene fusion. The American journal of surgical pathology 35 25353281
2015 Transcription Factor CREB3L1 Regulates Endoplasmic Reticulum Stress Response Genes in the Osmotically Challenged Rat Hypothalamus. PloS one 35 25915053
2014 Increased susceptibility to dextran sulfate sodium-induced colitis in the endoplasmic reticulum stress transducer OASIS deficient mice. PloS one 35 24498426
2018 CREB3L1 as a potential biomarker predicting response of triple negative breast cancer to doxorubicin-based chemotherapy. BMC cancer 34 30103710
2016 DNA Hypermethylation of CREB3L1 and Bcl-2 Associated with the Mitochondrial-Mediated Apoptosis via PI3K/Akt Pathway in Human BEAS-2B Cells Exposure to Silica Nanoparticles. PloS one 34 27362941
2017 CREB3L1-mediated functional and structural adaptation of the secretory pathway in hormone-stimulated thyroid cells. Journal of cell science 33 29093023
2008 bZIP-Type transcription factors CREB and OASIS bind and stimulate the promoter of the mammalian transcription factor GCMa/Gcm1 in trophoblast cells. Nucleic acids research 33 18495750
2007 A novel ER stress transducer, OASIS, expressed in astrocytes. Antioxidants & redox signaling 33 17330990
2014 OASIS/CREB3L1 is epigenetically silenced in human bladder cancer facilitating tumor cell spreading and migration in vitro. Epigenetics 32 25625847
2009 Near eastern neolithic genetic input in a small oasis of the Egyptian Western Desert. American journal of physical anthropology 32 19425100
2009 Increased vulnerability of hippocampal pyramidal neurons to the toxicity of kainic acid in OASIS-deficient mice. Journal of neurochemistry 32 19549009
2023 C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway. Cardiovascular research 30 37603848
2015 OASIS modulates hypoxia pathway activity to regulate bone angiogenesis. Scientific reports 29 26558437
2013 Physiological functions of endoplasmic reticulum stress transducer OASIS in central nervous system. Anatomical science international 29 24242870
2018 Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy. Bone 27 29936144
2021 Primary Cilia in Glial Cells: An Oasis in the Journey to Overcoming Neurodegenerative Diseases. Frontiers in neuroscience 26 34658775
2003 Comparison of expression patterns between CREB family transcription factor OASIS and proteoglycan core protein genes during murine tooth development. Anatomy and embryology 26 12684764
2020 Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta. Orphanet journal of rare diseases 25 32234057
2019 A homozygous pathogenic missense variant broadens the phenotypic and mutational spectrum of CREB3L1-related osteogenesis imperfecta. Human molecular genetics 25 30657919
2015 The date palm tree rhizosphere is a niche for plant growth promoting bacteria in the oasis ecosystem. BioMed research international 25 25866759
2010 Distinct mechanisms are responsible for osteopenia and growth retardation in OASIS-deficient mice. Bone 25 21047569
2021 Chemical Profile, Antioxidant, Antimicrobial, and Anticancer Activities of the Water-Ethanol Extract of Pulicaria undulata Growing in the Oasis of Central Saudi Arabian Desert. Plants (Basel, Switzerland) 24 34579344
2020 Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer. Journal for immunotherapy of cancer 24 32843336
2014 Sclerosing epithelioid fibrosarcoma presenting as intraabdominal sarcomatosis with a novel EWSR1-CREB3L1 gene fusion. Human pathology 24 25123073
2023 p53-independent tumor suppression by cell-cycle arrest via CREB/ATF transcription factor OASIS. Cell reports 23 37178686
2020 Transcription factor Creb3l1 regulates the synthesis of prohormone convertase enzyme PC1/3 in endocrine cells. Journal of neuroendocrinology 23 32319174
2013 Transcriptional regulation of VEGFA by the endoplasmic reticulum stress transducer OASIS in ARPE-19 cells. PloS one 23 23383089
2016 Evaluation of OASIS QSAR Models Using ToxCast™ in Vitro Estrogen and Androgen Receptor Binding Data and Application in an Integrated Endocrine Screening Approach. Environmental health perspectives 22 27152837
2015 Identification of CREB3L1 as a Biomarker Predicting Doxorubicin Treatment Outcome. PloS one 22 26110425
2015 Transcription factor CREB3L1 mediates cAMP and glucocorticoid regulation of arginine vasopressin gene transcription in the rat hypothalamus. Molecular brain 22 26503226
2007 OASIS and molecular-replacement model completion. Acta crystallographica. Section D, Biological crystallography 22 17582170
2024 The Regulatory Network of CREB3L1 and Its Roles in Physiological and Pathological Conditions. International journal of medical sciences 21 38164349
2018 The Geographic Structure of Viruses in the Cuatro Ciénegas Basin, a Unique Oasis in Northern Mexico, Reveals a Highly Diverse Population on a Small Geographic Scale. Applied and environmental microbiology 21 29625974
2017 A Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: The Optimizing Antibiotic Strategies in Sepsis (OASIS) Study. Journal of the Pediatric Infectious Diseases Society 21 27147715
2014 Primary low-grade fibromyxoid sarcoma of the kidney in a child with the alternative EWSR1-CREB3L1 gene fusion. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 21 24896634
2016 cAMP-Response Element-Binding 3-Like Protein 1 (CREB3L1) is Required for Decidualization and its Expression is Decreased in Women with Endometriosis. Current molecular medicine 19 26917262
2011 Roles of the endoplasmic reticulum stress transducer OASIS in fracture healing. Bone 19 21708301
2006 Clostridium schirmacherense sp. nov., an obligately anaerobic, proteolytic, psychrophilic bacterium isolated from lake sediment of Schirmacher Oasis, Antarctica. International journal of systematic and evolutionary microbiology 19 16585682
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2020 Chemotherapy Controls Metastasis Through Stimulatory Effects on GRP78 and Its Transcription Factor CREB3L1. Frontiers in oncology 18 33042795
2019 The first family with adult osteogenesis imperfecta caused by a novel homozygous mutation in CREB3L1. Molecular genetics & genomic medicine 18 31207160
2018 Primary Renal Hybrid Low-grade Fibromyxoid Sarcoma-Sclerosing Epithelioid Fibrosarcoma: An Unusual Pediatric Case With EWSR1-CREB3L1 Fusion. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 17 29426275
2011 Manufactured RBC--rivers of blood, or an oasis in the desert? Biotechnology advances 16 21609758
2020 Implementation of a Pragmatic Biomarker-Driven Algorithm to Guide Antibiotic Use in the Pediatric Intensive Care Unit: the Optimizing Antibiotic Strategies in Sepsis (OASIS) II Study. Journal of the Pediatric Infectious Diseases Society 15 30476186
2018 Effects of land use/cover on surface water pollution based on remote sensing and 3D-EEM fluorescence data in the Jinghe Oasis. Scientific reports 15 30166565
2017 Regulation of cAMP Responsive Element Binding Protein 3-Like 1 (Creb3l1) Expression by Orphan Nuclear Receptor Nr4a1. Frontiers in molecular neuroscience 15 29311806
2009 Effects of the bisphosphonate risedronate on osteopenia in OASIS-deficient mice. Journal of bone and mineral metabolism 15 20024590
2002 Expression of OASIS, a CREB/ATF family transcription factor, in CNS lesion and its transcriptional activity. Brain research. Molecular brain research 15 12480185
2024 Achievement of Clinical, Endoscopic, and Histological Outcomes in Patients with Ulcerative Colitis Treated with Etrasimod, and Association with Faecal Calprotectin and C-reactive Protein: Results From the Phase 2 OASIS Trial. Journal of Crohn's & colitis 14 38245818
2024 Design of OASIS 1 and 2: phase 3 clinical trials assessing the efficacy and safety of elinzanetant for the treatment of vasomotor symptoms associated with menopause. Menopause (New York, N.Y.) 14 38564691
2021 Induction of cell death in ovarian cancer cells by doxorubicin and oncolytic vaccinia virus is associated with CREB3L1 activation. Molecular therapy oncolytics 14 34632049
2020 In vitro anticancer activity of methanolic extract of Granulocystopsis sp., a microalgae from an oligotrophic oasis in the Chihuahuan desert. PeerJ 14 32201642
2022 How do bacteria transform plants into their oasis? Cell host & microbe 13 35421331
2017 Complete Mitochondrial Genome Sequencing of a Burial from a Romano-Christian Cemetery in the Dakhleh Oasis, Egypt: Preliminary Indications. Genes 13 28984839
2012 Gliosis-specific transcription factor OASIS coincides with proteoglycan core protein genes in the glial scar and inhibits neurite outgrowth. Biomedical research (Tokyo, Japan) 13 23268958
1999 Implications of the Organization to Assess Strategies for Ischemic Syndromes-2 (OASIS-2) study and the results in the context of other trials. The American journal of cardiology 13 10505540
2023 Tissue-resident memory T cells in gastrointestinal tumors: turning immune desert into immune oasis. Frontiers in immunology 12 36969190
2022 Isolation, Physiological Characterization, and Antibiotic Susceptibility Testing of Fast-Growing Bacteria from the Sea-Affected Temporary Meltwater Ponds in the Thala Hills Oasis (Enderby Land, East Antarctica). Biology 12 36009770
2014 OASIS regulates chondroitin 6-O-sulfotransferase 1 gene transcription in the injured adult mouse cerebral cortex. Journal of neurochemistry 12 24716865
2006 SAD phasing by OASIS-2004: case studies of dual-space fragment extension. Acta crystallographica. Section D, Biological crystallography 12 16855304
2024 Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial. Nature communications 11 39406730