Affinage

CREB3L1

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

Length
519 aa
Mass
57.0 kDa
Annotated
2026-06-09
100 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CREB3L1 (OASIS) is an endoplasmic reticulum-resident, transmembrane bZIP transcription factor that couples ER and secretory stress to a transcriptional program controlling secretory-cell differentiation, extracellular matrix production, and proliferative arrest (PMID:15665855, PMID:19767743). Under basal conditions it is held inactive: the transmembrane domain suppresses transcriptional activity and tethers the protein to the ER (PMID:12054625), and the ER-resident E3 ligase HRD1 ubiquitinates CREB3L1 to target it for proteasomal degradation (PMID:22705851). ER stress dissociates the HRD1 interaction and triggers translocation to the Golgi, where Site-1 and Site-2 Proteases cleave the protein by regulated intramembrane proteolysis, liberating the N-terminal bZIP fragment that enters the nucleus and activates targets through CRE/UPRE-like elements (PMID:16417584, PMID:22705851). Diverse upstream signals converge on this proteolytic switch: BMP2 accelerates CREB3L1 RIP during osteoblast differentiation (PMID:19767743), TGF-β induces cleavage by suppressing the inhibitor TM4SF20, after which the released fragment partners with Smad4 to drive collagen genes (PMID:25310401), ceramide generated in response to doxorubicin activates cleavage (PMID:23256041), and the PERK–eIF2α–ATF4 arm of the UPR feeds into CREB3L1 in vascular smooth muscle (PMID:37603848). Once nuclear, CREB3L1 directly transactivates a coherent set of targets including Col1a1 (PMID:19767743), the cell-cycle inhibitor p21 (PMID:23256041), VEGFA (PMID:23383089), Pcsk1 (PMID:32319174), and COPII components SEC23A/SEC24D (PMID:30657919), and it cooperates with HIF-1α via its bZIP domain to drive hypoxia-responsive angiogenic genes (PMID:26558437). Through these targets CREB3L1 governs osteoblast collagen secretion and bone formation (PMID:19767743, PMID:21047569), astrocyte and goblet-cell differentiation (PMID:22828627, PMID:22262831), secretory-pathway and Golgi expansion in secretory cells (PMID:29093023, PMID:36313580), DNA-damage-induced G2/M arrest (PMID:37178686), and antiviral/antiproliferative responses (PMID:21767813), while acting as a metastasis suppressor in some carcinomas yet a pro-invasive effector downstream of PERK in others (PMID:24126059, PMID:29057869, PMID:36192735). An uncleaved, full-length pool of CREB3L1 additionally accumulates at damaged nuclear envelopes with LINC-complex components SUN2 and Nesprin-2 to suppress DNA damage (PMID:34226518). Loss-of-function and bZIP-domain missense variants of CREB3L1 cause osteogenesis imperfecta, mechanistically linked to impaired type I collagen and SEC24D-dependent secretion (PMID:30657919, PMID:28817112).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1999 Medium

    Establishing that a CREB/ATF-family factor with a transmembrane domain is induced by CNS injury hinted that this transcription factor is regulated by membrane localization rather than constitutive nuclear residence.

    Evidence Differential display and in situ hybridization in astrocytes, mouse embryo, and injured brain

    PMID:10350641

    Open questions at the time
    • No functional assay of the protein
    • Mechanism of activation unknown
    • Target genes not identified
  2. 2002 Medium

    Mapping the autoinhibitory role of the transmembrane domain answered how the factor is kept inactive, showing membrane tethering suppresses CRE-dependent transcription until released.

    Evidence GAL4-luciferase reporters, gel shift, and localization with deletion constructs in COS7 cells

    PMID:12054625

    Open questions at the time
    • Physiological cleavage mechanism not defined
    • Endogenous targets not shown
    • No demonstration of stress regulation
  3. 2005 High

    Demonstrating ER-stress-induced cleavage and nuclear translocation established CREB3L1 as a membrane-bound UPR transcription factor that protects against ER-stress-induced death.

    Evidence Cleavage and translocation assays, reporter assays, siRNA knockdown and overexpression in astrocytes

    PMID:15665855

    Open questions at the time
    • Identity of cleaving proteases not yet established
    • Full UPR target spectrum unknown
  4. 2006 High

    Identifying S1P and S2P as the processing proteases at the Golgi defined the regulated intramembrane proteolysis mechanism and distinguished CREB3L1 from ATF6 by its lack of a canonical Golgi localization signal.

    Evidence Protease inhibitor assays, deletion mutagenesis, and subcellular localization in transfected cells

    PMID:16417584

    Open questions at the time
    • ER-to-Golgi trafficking trigger not defined
    • Regulation of protease access unknown
  5. 2009 High

    Knockout and Col1a1 promoter studies established the in vivo role of CREB3L1 in osteoblast collagen secretion and bone formation, linking BMP2 signaling to its proteolytic activation.

    Evidence OASIS-/- mice, promoter reporter, ChIP, histology, and BMP2 treatment

    PMID:19767743

    Open questions at the time
    • Whether bone phenotype is fully osteoblast-autonomous not yet resolved
    • Other matrix targets not mapped
  6. 2010 High

    Osteoblast-specific transgenic rescue separated the cell-autonomous bone phenotype from a systemic growth phenotype, refining where CREB3L1 acts in skeletal biology.

    Evidence Transgenic rescue under Col1a1 promoter, histology, RT-PCR, GH/IGF-1 ELISA in OASIS-/- mice

    PMID:21047569

    Open questions at the time
    • Mechanism of the osteoblast-independent growth defect unresolved
    • GH/IGF-1 regulatory link not mechanistically defined
  7. 2012 High

    Discovering HRD1-mediated ubiquitination and its dissociation under ER stress explained how CREB3L1 abundance is gated, adding a degradation layer upstream of proteolytic activation.

    Evidence Co-IP, in vitro ubiquitination assays, HRD1 knockout cells, and stability assays

    PMID:22705851

    Open questions at the time
    • Signal that disrupts HRD1 binding not defined
    • Relative contribution of degradation vs RIP unclear
  8. 2012 High

    Knockout analyses extended CREB3L1 function to astrocyte and goblet-cell differentiation, identifying Gcm1 and epigenetic Gfap demethylation as a downstream differentiation axis.

    Evidence Oasis-/- mice, primary culture, Gcm1 rescue, Gfap promoter methylation, and goblet cell histology

    PMID:22262831 PMID:22828627

    Open questions at the time
    • Direct binding of CREB3L1 to all differentiation targets not fully mapped
    • Tissue specificity of target selection unexplained
  9. 2011 High

    Showing virus-induced proteolytic activation and antiproliferative gene induction revealed CREB3L1 as an antiviral effector restricting host-cell proliferation needed for replication.

    Evidence Permissive/non-permissive cell comparison, viral infection, translocation imaging, knockdown and complementation

    PMID:21767813

    Open questions at the time
    • Sensor linking infection to cleavage not identified
    • Breadth of cell-cycle targets incomplete
  10. 2012 High

    Linking ceramide-driven cleavage to p21 induction connected a chemotherapy stress signal to CREB3L1-dependent cell-cycle arrest and drug sensitivity.

    Evidence Ceramide synthesis and cleavage assays, p21 reporter, knockdown and overexpression in cancer lines

    PMID:23256041

    Open questions at the time
    • How ceramide promotes ER-to-Golgi trafficking unclear
    • p53-independence not yet examined
  11. 2013 High

    Identifying CREB3L1 as a metastasis suppressor and a direct VEGFA activator established opposing roles in tumor biology and angiogenesis, with direct CRE-like promoter binding.

    Evidence Overexpression, invasion/migration assays, rat mammary tumor model, ChIP-on-chip; VEGFA promoter ChIP and mutant reporters in ARPE-19 cells

    PMID:23383089 PMID:24126059

    Open questions at the time
    • Context determining suppressor vs promoter role unknown
    • Direct angiogenic target set incompletely defined
  12. 2014 High

    Defining the TGF-β→TM4SF20→RIP→Smad4 axis and astrocyte ECM regulation showed how CREB3L1 partners with other factors to drive collagen and chondroitin sulfate matrix programs.

    Evidence TGF-β treatment, TM4SF20 manipulation, cleavage assay, CREB3L1–Smad4 Co-IP; C6ST1 reporter and neurite outgrowth assays in OASIS-/- mice; glycosylation mapping

    PMID:23335989 PMID:24716865 PMID:25310401

    Open questions at the time
    • Generality of Smad4 cooperation across cell types unknown
    • Functional role of Asn-513 glycosylation undefined
  13. 2015 High

    Hypothalamic and HIF-1α studies revealed neuroendocrine UPR control and a bZIP-mediated CREB3L1–HIF-1α partnership driving angiogenic transcription.

    Evidence Dominant-negative/shRNA in rat SON, UPR marker RT-PCR, forskolin/dexamethasone assays; CREB3L1–HIF-1α Co-IP, HRE reporters, metatarsal angiogenesis in Oasis-/- mice

    PMID:25915053 PMID:26503226 PMID:26558437

    Open questions at the time
    • Selectivity for Chop/Xbp1U over other UPR genes unexplained
    • Stoichiometry of CREB3L1–HIF-1α complex unknown
  14. 2016 Medium

    Knockdown in endometrial stromal cells placed CREB3L1 downstream of progesterone receptor signaling in decidualization, linking it to ERK1/2 activation.

    Evidence siRNA in hESCs, decidualization assay, ERK1/2 phosphorylation, PR knockout mouse

    PMID:26917262

    Open questions at the time
    • Direct decidualization targets not identified
    • Mechanism connecting CREB3L1 to ERK unclear
  15. 2017 High

    TSH-driven secretory-pathway expansion and PERK-dependent breast cancer invasion studies established CREB3L1 as a master regulator of Golgi/secretory capacity that can be co-opted to promote metastasis in specific tumor subtypes.

    Evidence Dominant-negative CREB3L1 with Golgi morphometry in thyroid cells; genetic/pharmacological CREB3L1 inhibition with PERK epistasis in TNBC models

    PMID:29057869 PMID:29093023

    Open questions at the time
    • Transport-factor target genes only partially enumerated
    • Determinants of pro- vs anti-tumor outcome unresolved
  16. 2017 Medium

    Functional characterization of a bZIP missense variant (p.Ala304Val) and DNA-binding variants linked CREB3L1 loss-of-function to osteogenesis imperfecta through impaired collagen and SEC24D-dependent secretion.

    Evidence Structural modeling, luciferase assays, mutant overexpression, and SEC23A/SEC24D expression in patient-derived cells; exome sequencing

    PMID:28817112 PMID:30657919

    Open questions at the time
    • Genotype–phenotype correlation across families incomplete
    • Quantitative contribution of SEC24D loss to OI severity unclear
  17. 2020 Medium

    Identifying Pcsk1 as a direct G-box target in the SON extended CREB3L1's neuroendocrine role to proprotein convertase expression.

    Evidence RNA-seq, promoter activity and binding assays, lentiviral overexpression/knockdown in rat SON

    PMID:32319174

    Open questions at the time
    • Physiological consequence of Pcsk1 regulation not measured
    • Single lab
  18. 2021 Medium

    Discovering that full-length, uncleaved CREB3L1 accumulates at damaged nuclear envelopes revealed a transcription-independent function in nuclear envelope/DNA damage protection distinct from its UPR role.

    Evidence Live-cell and IF imaging of NE damage, colocalization with SUN2/Nesprin-2, DNA damage and nuclear deformation assays

    PMID:34226518

    Open questions at the time
    • Molecular mechanism of NE protection undefined
    • How full-length form is selectively retained unclear
    • Single lab
  19. 2022 High

    Thyroid cancer and decidualization studies clarified how CREB3L1 drives invasion via ECM/IL-1α-mediated CAF activation (with KPNA2 as nuclear import factor) and how CREB3L1/CREB3L2 together sustain Golgi expansion and secretion.

    Evidence Knockdown/overexpression, cytokine array, scRNA-seq, zebrafish/mouse xenografts, co-culture; combined CREB3L1/CREB3L2 knockdown with Golgi and secretion assays

    PMID:36192735 PMID:36313580

    Open questions at the time
    • Redundancy boundaries between CREB3L1 and CREB3L2 not fully mapped
    • Direct IL-1α promoter regulation not shown
  20. 2023 High

    Defining a cell-type-specific p21-dependent G2/M arrest and the C5a-PERK-ATF4-CREB3L1 calcification axis unified CREB3L1's roles in proliferation control and osteogenic transdifferentiation, with epigenetic reactivation suppressing glioblastoma growth.

    Evidence Oasis-/- mice, flow cytometry, p21 reporter, p53-null comparison, brain injury and CRISPR epigenomic xenograft models; VSMC calcification with C5aR1 antagonist

    PMID:37178686 PMID:37603848

    Open questions at the time
    • Basis of cell-type dominance of CREB3L1 vs p53 arrest unexplained
    • Therapeutic window of epigenetic reactivation undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CREB3L1 trafficking, cleavage, and target selection are differentially tuned across cell types to produce opposite outcomes (tumor suppression vs promotion; transcriptional vs nuclear-envelope-protective roles) remains the central open question.
  • No structural model of the activated bZIP fragment bound to DNA or HIF-1α/Smad4
  • Determinants of context-dependent function unknown
  • Trigger for ER-to-Golgi translocation incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 5 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0005634 nucleus 3 GO:0005783 endoplasmic reticulum 3 GO:0005635 nuclear envelope 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1474244 Extracellular matrix organization 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 2 R-HSA-1643685 Disease 2
Partners
HIF1AHRD1KPNA2SMAD4SUN2SYNE2TM4SF20

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 OASIS/CREB3L1 was identified as a novel CREB/ATF family transcription factor with a transmembrane domain, specifically induced in long-term cultured astrocytes and gliotic tissue; its expression is developmentally regulated and induced by CNS injury. Differential display screening, in situ hybridization, expression analysis in mouse embryo and injured brain Brain research. Molecular brain research Medium 10350641
2002 OASIS functions as a transcriptional activator through CRE binding; the transmembrane domain suppresses transcriptional activity and retains OASIS in the ER, while truncation of the transmembrane domain increases transcriptional activity and relocates OASIS to the nucleus. GAL4-UAS-luciferase reporter assay, gel shift assay, subcellular localization by Western blot, deletion constructs in COS7 cells Biochemical and biophysical research communications Medium 12054625
2005 OASIS/CREB3L1 is a membrane-bound ER-resident transcription factor that is cleaved at the membrane in response to ER stress, releasing its cytoplasmic bZIP-containing N-terminal domain to translocate to the nucleus where it activates target genes via ER stress-responsive and cAMP-responsive elements; knockdown reduced BiP levels and exacerbated ER stress in astrocytes, while overexpression induced BiP and suppressed ER-stress-induced cell death. Membrane cleavage assay, nuclear translocation imaging, reporter gene assay, knockdown (siRNA), overexpression in astrocytes Nature cell biology High 15665855
2006 OASIS/CREB3L1 is processed by Site-1 Protease (S1P) and Site-2 Protease (S2P) at the Golgi apparatus in response to ER stress, similar to ATF6; cleavage is triggered by translocation of OASIS from the ER to the Golgi, but unlike ATF6, luminal domain deletion mutants retain intact proteolytic processing, indicating OASIS lacks a canonical Golgi localization signal. Protease inhibitor assays, deletion mutagenesis, subcellular fractionation/localization in transfected cells Journal of neurochemistry High 16417584
2008 OASIS/CREB3L1 binds and stimulates the promoter of the transcription factor GCMa/Gcm1 in trophoblast cells; knockdown of endogenous OASIS in BeWo cells decreased endogenous GCMa mRNA level and activity, and overexpression of OASIS led to placental cell fusion accompanied by connexin-43 expression. Promoter mapping, reporter assays, knockdown (siRNA), overexpression, and cell fusion assays in trophoblast cells Nucleic acids research Medium 18495750
2009 OASIS/CREB3L1 activates transcription of Col1a1 (type I collagen) through a UPRE-like sequence in the osteoblast-specific promoter; OASIS-/- mice exhibit severe osteopenia with decreased type I collagen in bone matrix and abnormally expanded rough ER in osteoblasts; BMP2 signaling induces OASIS expression and accelerates its regulated intramembrane proteolysis (RIP), causing mild ER stress. Knockout mouse model, promoter reporter assay, ChIP, RT-PCR, histological analysis, BMP2 treatment Nature cell biology High 19767743
2010 Osteoblast-specific re-expression of OASIS in OASIS-/- mice rescues osteopenia and normalizes type I collagen mRNA and rough ER morphology, confirming the osteoblast-autonomous role; growth retardation in OASIS-/- mice is not rescued by osteoblast-specific OASIS and is associated with reduced serum GH and IGF-1, indicating an osteoblast-independent mechanism for this phenotype. Transgenic rescue (osteoblast-specific OASIS expression under 2.3-kb Col1a1 promoter), histology, RT-PCR, ELISA for GH and IGF-1 Bone High 21047569
2011 OASIS/CREB3L1 is proteolytically activated in response to infection by multiple viruses (murine γ-herpesvirus 68, HCV, West Nile virus, Sendai virus), allowing its N-terminus to enter the nucleus and induce cell cycle inhibitor genes to block cell proliferation; cells harboring HCV or WNV replicons require OASIS silencing to proliferate. Gene expression comparison between permissive/non-permissive cell lines, virus infection assays, nuclear translocation imaging, gene expression profiling, knockdown and complementation Cell host & microbe High 21767813
2012 OASIS/CREB3L1 and other OASIS family members are unstable proteins degraded via the ubiquitin-proteasome pathway under normal conditions; HRD1 (an ER-resident E3 ubiquitin ligase) ubiquitinates OASIS under normal conditions; ER stress dissociates the HRD1-OASIS interaction and stabilizes OASIS, enhancing target gene transcription. Co-immunoprecipitation, ubiquitination assays, HRD1 knockout cells, stability assays in transfected cells Cell death and differentiation High 22705851
2012 OASIS/CREB3L1 is required for differentiation of neural precursor cells into astrocytes; Oasis-/- mice have fewer astrocytes and more neural precursor cells during cortical development; the transcription factor Gcm1 was identified as an OASIS target gene required for astrocyte differentiation, and introduction of Gcm1 into Oasis-/- cells rescued differentiation by promoting demethylation of the Gfap promoter. Knockout mouse analysis, primary cell culture, Gcm1 rescue experiment, Gfap promoter methylation assay, interaction studies among OASIS family members Nature communications High 22828627
2012 OASIS/CREB3L1 is required for terminal differentiation of goblet cells in the large intestine; Oasis-/- mice show reduced goblet cell number and mucus production, impaired maturation from early to mature goblet cells, abnormal mucous vesicles and rough ER; OASIS is activated by mild ER stress during goblet cell differentiation. Knockout mouse analysis, histology, goblet cell marker expression, knockdown in cell culture differentiation model The Journal of biological chemistry High 22262831
2012 Doxorubicin stimulates ceramide synthesis, which activates CREB3L1 through 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 resistance to doxorubicin, while overexpression enhances sensitivity. Ceramide synthesis assay, proteolytic cleavage assay, nuclear translocation imaging, p21 reporter assay, KD and OE in cancer cell lines eLife High 23256041
2013 CREB3L1 acts as a metastasis suppressor in breast cancer; re-expression in metastatic cells reduces invasion and migration in vitro and suppresses metastasis in vivo; ChIP-on-chip analysis identified CREB3L1 target genes including those regulating angiogenesis; tumor regression involved impaired angiogenesis. Transfection/overexpression, invasion and migration assays, in vivo rat mammary tumor model, microarray, ChIP-on-chip Molecular and cellular biology High 24126059
2013 OASIS/CREB3L1 promotes VEGFA expression in human retinal pigment epithelial cells (ARPE-19) by directly binding to a CRE-like site at approximately -500 bp in the VEGFA promoter, as demonstrated by reporter assays with deletion/mutation constructs and chromatin immunoprecipitation. Reporter assay with deletion and point mutant constructs, chromatin immunoprecipitation (ChIP), ER stress induction in ARPE-19 cells PloS one High 23383089
2013 OASIS/CREB3L1 knockdown in human glioma cells attenuates the UPR (reduced BiP/GRP78 and GRP94 induction), decreases expression of chondroitin sulfate proteoglycan extracellular matrix proteins, and reduces cell migration; OASIS protein is glycosylated on Asn-513. Knockdown (siRNA), ER stress induction, gene expression analysis, migration assay, glycosylation mapping PloS one Medium 23335989
2014 TGF-β induces proteolytic activation of CREB3L1 by suppressing expression of TM4SF20, which normally inhibits RIP of CREB3L1; the released N-terminal domain of CREB3L1 enters the nucleus and binds to Smad4 to activate transcription of collagen extracellular matrix genes. TGF-β treatment, TM4SF20 expression/knockdown, CREB3L1 cleavage assay, co-immunoprecipitation of CREB3L1 and Smad4, collagen gene reporter assay PloS one High 25310401
2014 OASIS regulates transcription of chondroitin 6-O-sulfotransferase 1 (C6ST1) in reactive astrocytes of injured cortex by interacting with the first intron of the C6ST1 gene; OASIS knockout mice show reduced CSPG sulfation after stab injury, and membrane fractions from OASIS-expressing astrocytes inhibit neurite outgrowth via CSPGs. OASIS knockout mouse model, in situ hybridization, RT-PCR, C6ST1 reporter assay with deletion constructs, neurite outgrowth assay with chondroitinase ABC treatment Journal of neurochemistry High 24716865
2015 CREB3L1 in the rat hypothalamus acts as a transcriptional regulator of ER stress response genes (Chop, Xbp1U) in osmotically challenged magnocellular neurons; dominant-negative CREB3L1 expressed via lentiviral vector in the SON reduced Chop and Xbp1U mRNA but not BiP or Atf4, establishing CREB3L1 as a selective mediator of the UPR in these neurons. Lentiviral dominant-negative expression in rat SON in vivo, RT-PCR for UPR markers, dehydration/salt-loading model PloS one Medium 25915053
2015 OASIS/CREB3L1 N-terminal fragment (activated form) binds to HIF-1α through its bZIP domain, as shown by co-immunoprecipitation; this interaction promotes transcription via hypoxia-response elements (HRE) including VEGFA; OASIS-deficient mice show reduced Vegfa expression in osteoblasts and retarded bone vascularization. Co-immunoprecipitation, luciferase reporter assay (HRE), RT-PCR, immunostaining, metatarsal angiogenesis assay in Oasis-/- mice Scientific reports High 26558437
2015 CREB3L1 mediates cAMP positive regulation and glucocorticoid negative regulation of arginine vasopressin (AVP) gene transcription in the rat hypothalamus; shRNA silencing of Creb3l1 blunts forskolin-induced Avp promoter activity; in vivo dexamethasone reduces Creb3l1 and Avp expression induced by hyperosmotic stress. shRNA knockdown, cAMP elevation (forskolin), dexamethasone treatment, promoter reporter assay in AtT20 cells and hypothalamic organotypic cultures, in vivo injections Molecular brain Medium 26503226
2016 CREB3L1 is required for the decidualization of human endometrial stromal cells (hESCs); siRNA knockdown of CREB3L1 impairs hormonal induction of decidualization and reduces phosphorylation of ERK1/2; CREB3L1 expression is regulated by progesterone receptor (PR) signaling in the mouse uterus. siRNA knockdown in hESCs, in vitro decidualization assay, ERK1/2 phosphorylation assay, PR knockout mouse model, progesterone treatment Current molecular medicine Medium 26917262
2017 CREB3L1 functions downstream of PERK signaling specifically in mesenchymal triple-negative breast cancer to drive invasion and metastasis; genetic or pharmacological inhibition of CREB3L1 suppresses cancer cell invasion and metastasis in this tumor subtype. Genetic knockdown/knockout of CREB3L1, pharmacological inhibition, in vitro invasion assays, in vivo metastasis models, epistasis with PERK inhibition Nature communications High 29057869
2017 CREB3L1 acts as a downstream effector of TSH (thyrotropin) in thyroid cells to regulate secretory pathway expansion; CREB3L1 alone increases expression of ER-Golgi transport factors and induces Golgi enlargement; a dominant-negative CREB3L1 construct impairs TSH-induced Golgi expansion. TSH stimulation, dominant-negative CREB3L1 expression, Golgi morphology analysis (volume quantification), transport factor mRNA/protein measurement in thyroid cells Journal of cell science High 29093023
2017 A missense variant in the bZIP domain of CREB3L1 (p.Ala304Val) decreases type I collagen transcriptional binding ability as shown by in vitro structural modeling and luciferase assays; overexpression of mutant OASIS also decreases transcription of SEC23A and SEC24D (COPII complex components) and reduces SEC24D protein levels. In vitro structural modeling, luciferase reporter assay, overexpression of mutant OASIS, qRT-PCR and Western blot for SEC23A/SEC24D in patient-derived cells Human molecular genetics Medium 30657919
2017 The CREB3L1 variant that disrupts the DNA-binding site prevents OASIS from acting on its transcriptional targets including SEC24D (a COPII complex component), linking CREB3L1-associated OI to impaired regulation of proteins involved in cellular secretion. Exome sequencing, functional characterization of DNA-binding variant, target gene (SEC24D) transcription analysis in patient cells Genetics in medicine Medium 28817112
2020 CREB3L1 directly binds to a G-box motif in the Pcsk1 promoter to activate transcription of the proprotein convertase PC1/3; lentiviral overexpression of Creb3l1 in rat SON increased Pcsk1, while knockdown decreased Pcsk1 expression; in vitro promoter activity and binding studies confirmed direct transcription factor binding. RNA-sequencing of Creb3l1 knockdown cells, in vitro promoter activity assay, binding studies, lentiviral overexpression/knockdown in rat SON in vivo, RT-qPCR Journal of neuroendocrinology Medium 32319174
2021 OASIS/CREB3L1 accumulates at damaged nuclear envelope (NE) in a full-length (uncleaved) form—distinct from its ER stress response as a cleaved fragment—and colocalizes with SUN2 and Nesprin-2 (LINC complex components) at damaged NE; OASIS suppresses DNA damage induced by NE stress and restores nuclear deformation; this NE accumulation is specific to OASIS among OASIS family members. Live-cell and immunofluorescence imaging of NE damage, colocalization with LINC complex proteins and NE repair factors, DNA damage assay, nuclear deformation measurement, comparison with other OASIS family members Cell death discovery Medium 34226518
2022 CREB3L1 promotes ATC invasion and metastasis by activating extracellular matrix signaling including collagen subtype expression; KPNA2 mediates nuclear translocation of CREB3L1; CREB3L1-mediated IL-1α production activates α-SMA-positive cancer-associated fibroblasts (CAFs); loss of CREB3L1 prevents CAF activation and suppresses ATC metastasis in zebrafish and mouse xenograft models. Knockdown/overexpression of CREB3L1, cytokine array, zebrafish and mouse xenograft models, single-cell RNA-seq analysis, co-culture of ATC cells and fibroblasts, ECM/collagen quantification Molecular cancer High 36192735
2022 CREB3L1 and CREB3L2 are both required for Golgi enlargement during decidualization of endometrial stromal cells; simultaneous knockdown of CREB3L1 and CREB3L2 causes Golgi fragmentation, collagen accumulation in dilated ER, and decreased protein secretion; CREB3L1/CREB3L2 binding elements are enriched in promoters of co-regulated vesicular trafficking genes upregulated during decidualization. Time-course transcriptomic analysis, promoter motif analysis, simultaneous CREB3L1/CREB3L2 knockdown, Golgi morphology quantification, collagen immunofluorescence, protein secretion assay Frontiers in cell and developmental biology Medium 36313580
2023 OASIS/CREB3L1 arrests the cell cycle at G2/M phase after DNA damage via direct induction of p21; this G2/M arrest is dominant in astrocytes and osteoblasts but not fibroblasts, which depend on p53; in a brain injury model, Oasis-/- reactive astrocytes show sustained proliferation and prolonged gliosis; epigenomic reversal of CREB3L1 promoter hypermethylation in glioblastoma xenografts suppresses tumor growth. Knockout mouse model, cell cycle analysis (flow cytometry), p21 reporter assay, p53-null comparison, brain injury model, CRISPR-based epigenomic engineering in xenograft model Cell reports High 37178686
2023 C5a-C5aR1 activates the PERK-eIF2α-ATF4-CREB3L1 ER stress pathway in vascular smooth muscle cells; CREB3L1 acts as a key downstream mediator that promotes COL1α1 expression to drive osteogenic transdifferentiation and vascular calcification. VSMCs calcification models in vitro, C5aR1 antagonist (PMX 53) in vivo, calcium deposition assay, Western blot/RT-PCR for pathway components, COL1α1 expression Cardiovascular research Medium 37603848

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 295 19767743
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 247 24812292
2005 OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes. Nature cell biology 247 15665855
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 220 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 123 16417584
2017 Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1. Nature communications 117 29057869
2014 Recurrent EWSR1-CREB3L1 gene fusions in sclerosing epithelioid fibrosarcoma. The American journal of surgical pathology 117 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 97 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
2022 CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment. Molecular cancer 94 36192735
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 94 16618921
2000 The Santa Barbara Basin is a symbiosis oasis. Nature 93 10638755
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 89 33475734
1989 Isolation and identification of Pseudomonas spp. from Schirmacher Oasis, Antarctica. Applied and environmental microbiology 81 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
2024 Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA 71 39172446
2011 Physiological unfolded protein response regulated by OASIS family members, transmembrane bZIP transcription factors. IUBMB life 70 21438114
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 60 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
2016 Cancer Cell-Derived Extracellular Vesicles Are Associated with Coagulopathy Causing Ischemic Stroke via Tissue Factor-Independent Way: The OASIS-CANCER Study. PloS one 55 27427978
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
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 46 20668028
2017 High diversity and suggested endemicity of culturable Actinobacteria in an extremely oligotrophic desert oasis. PeerJ 44 28480140
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
2015 Primary renal sclerosing epithelioid fibrosarcoma: report of 2 cases with EWSR1-CREB3L1 gene fusion. The American journal of surgical pathology 36 25353281
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 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
2007 A novel ER stress transducer, OASIS, expressed in astrocytes. Antioxidants & redox signaling 34 17330990
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
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 31 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
2021 Primary Cilia in Glial Cells: An Oasis in the Journey to Overcoming Neurodegenerative Diseases. Frontiers in neuroscience 28 34658775
2018 Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy. Bone 27 29936144
2020 Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta. Orphanet journal of rare diseases 26 32234057
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 Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer. Journal for immunotherapy of cancer 25 32843336
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
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 24 27147715
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
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 23 27152837
2013 Transcriptional regulation of VEGFA by the endoplasmic reticulum stress transducer OASIS in ARPE-19 cells. PloS one 23 23383089
2024 The Regulatory Network of CREB3L1 and Its Roles in Physiological and Pathological Conditions. International journal of medical sciences 22 38164349
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
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
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 20 26917262
2011 Roles of the endoplasmic reticulum stress transducer OASIS in fracture healing. Bone 20 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
2021 OASIS/CREB3L1 is a factor that responds to nuclear envelope stress. Cell death discovery 18 34226518
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
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 16 30476186
2011 Manufactured RBC--rivers of blood, or an oasis in the desert? Biotechnology advances 16 21609758
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 15 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.) 15 38564691
2020 In vitro anticancer activity of methanolic extract of Granulocystopsis sp., a microalgae from an oligotrophic oasis in the Chihuahuan desert. PeerJ 15 32201642
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
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
2012 Gliosis-specific transcription factor OASIS coincides with proteoglycan core protein genes in the glial scar and inhibits neurite outgrowth. Biomedical research (Tokyo, Japan) 14 23268958
2024 Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial. Nature communications 13 39406730
2022 How do bacteria transform plants into their oasis? Cell host & microbe 13 35421331
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
2022 CREB3L1 and CREB3L2 control Golgi remodelling during decidualization of endometrial stromal cells. Frontiers in cell and developmental biology 12 36313580
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

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