Affinage

PREB

Guanine nucleotide-exchange factor SEC12 · UniProt Q9HCU5

Length
417 aa
Mass
45.5 kDa
Annotated
2026-06-10
100 papers in source corpus 11 papers cited in narrative 11 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PREB/SEC12 is the guanine nucleotide exchange factor (GEF) for the small GTPase Sar1 and serves as the initiating factor for COPII-dependent ER-to-Golgi vesicle budding, a role conserved from yeast and plants to mammals (PMID:8377826, PMID:1396601). Its catalytically active cytoplasmic domain folds into a β-propeller whose conserved, potassium-stabilized 'K loop' is essential for nucleotide exchange on Sar1, while GTP hydrolysis is driven in concert with the GAP Sec23 to recruit Sar1-GTP and seed coat assembly (PMID:8377826, PMID:23109340). SEC12 is dynamically concentrated at ER exit sites (transitional ER) through direct interaction with the C-terminal domain of Sec16, providing locally elevated Sar1-GTP generation at sites of cargo export (PMID:22347445, PMID:15130490). At these sites SEC12 directly binds the collagen cargo-receptor component cTAGE5 and is co-packaged with TANGO1 into large COPII carriers, a localized enrichment specifically required for export of bulky cargo such as collagen, while being excluded from small COPII vesicles (PMID:25202031, PMID:30545919). Under stress, SEC12 additionally engages TMED9 to form ERGIC–ERES membrane contacts that transactivate COPII assembly on the ERGIC to supply autophagosome precursor membrane (PMID:34561617). Separately, in pituitary cells the mammalian protein localizes to the nucleus and acts as a sequence-specific, PKA-responsive transcriptional activator of the prolactin promoter (PMID:10194769).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1992 High

    Established that the ER-to-Golgi budding factor encoded by Sec12 is functionally conserved across eukaryotes, indicating a universal vesicle-budding mechanism rather than a yeast-specific one.

    Evidence Heterologous complementation of a budding-yeast sec12 null by fission yeast and Arabidopsis homologues, with sequence analysis

    PMID:1396601

    Open questions at the time
    • Did not define the biochemical activity of the conserved domain
    • No direct evidence linking the conserved cytoplasmic domain to a specific GTPase
  2. 1993 High

    Defined the molecular activity of Sec12 as a GEF for Sar1 and placed it upstream of coat assembly, answering how vesicle budding is initiated at the ER.

    Evidence In vitro GEF and GTPase assays with purified proteins, Sec12-1 mutant comparison, and Sec12+Sec23 reconstitution in yeast

    PMID:8377826

    Open questions at the time
    • Structural basis of nucleotide exchange unresolved
    • Mechanism of spatial restriction to ER exit sites not addressed
  3. 1999 High

    Identified a distinct nuclear, transcriptional role for the mammalian protein, showing PREB acts as a PKA-responsive activator at the prolactin promoter — a function separate from its membrane GEF activity.

    Evidence Expression cloning from pituitary cDNA, DNA-binding gel shift, reporter transactivation, immunocytochemistry, and GAL4 fusion with PKA stimulation

    PMID:10194769

    Open questions at the time
    • Relationship between the nuclear transcriptional role and the ER membrane GEF role unresolved
    • No structural basis for promoter element 1P recognition
  4. 1999 Medium

    Revealed negative regulation of Sec12-dependent budding by a casein kinase I, showing the pathway is subject to kinase control.

    Evidence Genetic suppressor cloning of sec12-4 by kinase-dead Hrr25 alleles with kinase-activity confirmation and secretion assays in yeast

    PMID:9920934

    Open questions at the time
    • No direct substrate (Sec12 phosphorylation) demonstrated
    • Mechanism by which kinase activity inhibits budding undefined
    • Genetic epistasis only; not biochemically reconstituted
  5. 2003 Medium

    Placed Sec12 genetically upstream of Sar1 in the ER exit pathway and extended its role to a developmental membrane-assembly process (meiotic forespore formation).

    Evidence Genetic complementation, EM membrane morphology, Rer1 localization, and Sar1 overproduction suppression in S. pombe

    PMID:12631727

    Open questions at the time
    • Direct GEF activity not assayed in this system
    • Single-organism genetic epistasis
  6. 2004 Medium

    Showed Sec12 is dynamically and saturably concentrated at transitional ER via its cytosolic domain binding a pre-existing scaffold, addressing how the GEF is spatially organized.

    Evidence Live fluorescence imaging/photobleaching, domain truncation, and overexpression saturation in P. pastoris

    PMID:15130490

    Open questions at the time
    • The specific tER partner was not molecularly identified in this study
    • Single-lab imaging system
  7. 2012 High

    Identified Sec16 as the direct partner that concentrates Sec12 at tER sites, resolving the molecular basis of its spatial targeting in yeast and human cells.

    Evidence Overexpression-titration imaging, heterologous expression with/without Sec16, and pull-down between Sec16 C-terminus and Sec12 cytosolic domain

    PMID:22347445

    Open questions at the time
    • Quantitative contribution of Sec16 vs other partners to human Sec12 localization not dissected
    • Effect of the interaction on GEF activity not measured
  8. 2012 High

    Provided the structural mechanism of nucleotide exchange, defining the β-propeller fold and a potassium-stabilized K loop as catalytically essential.

    Evidence 1.36 Å crystal structure of the S. cerevisiae cytoplasmic domain with structure-guided mutagenesis and in vitro/in vivo GEF assays

    PMID:23109340

    Open questions at the time
    • No structure of the Sec12–Sar1 complex
    • Structure of the mammalian/full-length protein not determined
  9. 2014 High

    Established a cargo-specific function by showing ERES-concentrated SEC12, via direct cTAGE5 binding, is selectively required for collagen export.

    Evidence Reciprocal Co-IP of SEC12 and cTAGE5, siRNA knockdown with cargo-specific collagen secretion readout, and ERES localization imaging in human cells

    PMID:25202031

    Open questions at the time
    • Whether locally elevated Sar1-GTP alone explains cargo selectivity not directly measured
    • Generality across collagen subtypes and other bulky cargos not fully defined
  10. 2018 High

    Demonstrated that SEC12 co-packaging is causally required to generate the large COPII carriers needed for bulky procollagen cargo, linking its local enrichment to carrier size control.

    Evidence Vesicle budding/cargo fractionation, split-GFP reconstitution targeting SEC12 to procollagen via TANGO1, and imaging of SEC12 distribution around carriers

    PMID:30545919

    Open questions at the time
    • Mechanism converting local Sar1-GTP into membrane curvature/size remains incompletely defined
    • Quantitative stoichiometry on large carriers not established
  11. 2021 High

    Uncovered a stress-induced role in which SEC12, via direct TMED9 binding, builds ERGIC-ERES contacts that transactivate COPII on the ERGIC to supply autophagosome membrane, extending its function beyond secretory transport.

    Evidence Reciprocal Co-IP, EM inter-membrane distance measurement, siRNA knockdown with autophagy readout, and COPII assembly assay on ERGIC in human cells

    PMID:34561617

    Open questions at the time
    • Signal that triggers SEC12 relocalization to ERGIC unclear
    • How TMED9-mediated contact is regulated relative to secretory ERES function undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the mammalian protein's nuclear transcriptional activity and its ER membrane GEF activity are coordinated, and whether one pool regulates the other.
  • No study connects the prolactin-promoter transcriptional role to the COPII/ERES GEF role
  • No mechanism for partitioning PREB between nucleus and ER membrane

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2 GO:0003677 DNA binding 1 GO:0140110 transcription regulator activity 1
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005634 nucleus 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-74160 Gene expression (Transcription) 1 R-HSA-9612973 Autophagy 1
Partners
CTAGE5SAR1SEC16SEC23TANGO1TMED9
Complex memberships
COPII coatTANGO1/cTAGE5 collagen export complex

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Yeast Sec12 (PREB ortholog) encodes a guanine-nucleotide exchange factor (GEF) for the Sar1 GTPase: a purified cytoplasmic fragment of Sec12 promotes guanine-nucleotide dissociation from Sar1, while the temperature-sensitive mutant Sec12-1 retains only ~15% of wild-type GEF activity. GTP hydrolysis by Sar1 is not enhanced by Sec12 alone but is stimulated >50-fold by a mixture of Sec12 and the GAP Sec23, supporting a model in which Sec12 recruits Sar1-GTP to the ER membrane to initiate vesicle budding. In vitro GEF assay with purified recombinant proteins; mutant Sec12-1 activity comparison; GTPase assay with Sec12 + Sec23 Nature High 8377826
1992 Fission yeast Sec12 homologue (Stl1p/Spo14) and a plant Arabidopsis homologue (Stl2p) are functional homologues of budding yeast Sec12: their cytoplasmic domains resemble Sec12p and expression of either gene complements a sec12 null mutation, demonstrating conservation of the ER-to-Golgi vesicle budding mechanism across eukaryotes. Complementation of sec12 null mutation by heterologous cDNA expression; sequence analysis The EMBO journal High 1396601
1999 PREB (designated as such in mammals) was cloned from rat pituitary cDNA as a novel WD-motif protein that binds specifically to the prolactin (PRL) promoter element 1P in a sequence-specific manner (distinct from Pit-1 binding site). PREB localizes to the nucleus in GH3 pituitary cells and transactivates a PRL promoter construct in PREB-negative C6 cells; a GAL4-PREB fusion strongly transactivates a reporter and mediates further stimulation by protein kinase A (PKA), establishing PREB as a PKA-responsive transcriptional activator at the PRL promoter. Expression cloning from pituitary cDNA library; gel shift/DNA-binding assay; transient transfection reporter assay; Western blot and immunocytochemistry for nuclear localization; GAL4 fusion transactivation assay with and without PKA Molecular endocrinology High 10194769
2012 In Pichia pastoris, Sec12 is concentrated at transitional ER (tER) sites through a direct physical interaction with the C-terminal domain of Sec16. Overexpression of Sec12 alone delocalizes it to the general ER, but co-overexpression of Sec16 retains Sec12 at tER sites. Biochemical pull-down confirms that the C-terminal fragment of Sec16 binds the cytosolic domain of Sec12. Human Sec12 (PREB) is similarly concentrated at tER sites, likely via association with Sec16A. Fluorescence localization with overexpression titration; heterologous expression of P. pastoris Sec12 in S. cerevisiae with and without P. pastoris Sec16; biochemical binding assay (pull-down) between Sec16 C-terminal fragment and Sec12 cytosolic domain; human Sec12 localization by imaging PloS one High 22347445
2012 Crystal structure of the catalytically active cytoplasmic domain of S. cerevisiae Sec12 at 1.36 Å resolution reveals a β-propeller fold. A conserved 'K loop' extending from the N-terminal blade is catalytically essential for GEF activity toward Sar1; structure-guided mutagenesis of K-loop residues abolishes activity in vitro and in vivo. A bound potassium ion stabilizes the K loop and is required for optimal guanine nucleotide exchange activity. X-ray crystallography (1.36 Å); structure-guided site-directed mutagenesis; in vitro GEF assay; in vivo yeast functional assay The Journal of biological chemistry High 23109340
2004 In Pichia pastoris, Sec12 localizes to tER sites and exchanges rapidly between tER sites and the general ER (dynamic localization). The tER concentration of Sec12 is saturable and requires the cytosolic domain of Sec12 to interact with a tER partner component. Oligomerization of the Sec12 lumenal domain is required for efficient cytosolic-domain-mediated tER localization. Redistribution of Sec12 to the general ER does not perturb downstream tER components, suggesting Sec12 associates with a pre-existing tER scaffold. Fluorescence live imaging and photobleaching (FRAP-type); domain truncation and mutagenesis; overexpression saturation experiments Developmental cell Medium 15130490
2014 Human Sec12 (PREB) is concentrated at ER exit sites (ERES) through direct interaction with cTAGE5, a component of the TANGO1/cTAGE5 collagen cargo receptor complex at ERES. This concentration of Sec12 at ERES is specifically required for secretion of collagen VII but not other secretory proteins. Depletion of Sec12 from ERES (e.g., by cTAGE5 knockdown) selectively impairs collagen export, identifying a cargo-specific requirement for locally elevated Sar1-GTP generated by ERES-concentrated Sec12. Co-immunoprecipitation (direct interaction between Sec12 and cTAGE5); siRNA knockdown of cTAGE5/Sec12; collagen secretion assay; immunofluorescence localization of Sec12 at ERES The Journal of cell biology High 25202031
1999 In yeast, the kinase-dead (inactive) form of the casein kinase I Hrr25p suppresses the sec12-4 temperature-sensitive mutation. The suppressor allele hrr25-2 (T176I in kinase domain) has markedly reduced kinase activity, and overexpression of another kinase-dead Hrr25 mutant (K38A) also suppresses sec12-4. This indicates that Hrr25p kinase activity negatively regulates Sec12-dependent vesicle budding from the ER. Genetic suppressor cloning; kinase assay of immunoprecipitated Hrr25p mutant; growth and secretion assays in sec12-4 background The Journal of biological chemistry Medium 9920934
2003 The S. pombe Sec12 homologue Spo14/Stl1 is essential for ER-to-Golgi protein transport and for forespore membrane assembly during meiosis. In spo14 mutant cells, ER-like membranes accumulate and the ER/Golgi marker Rer1 is retained in the ER. Overproduction of the S. pombe Sar1 homologue Psr1 suppresses both the sporulation defect and cold-sensitive growth of spo14 mutants, placing Spo14/Sec12 upstream of Sar1 in the ER exit pathway. Genetic complementation; electron microscopy of membrane morphology; Rer1 localization assay; Sar1 overproduction suppression Molecular biology of the cell Medium 12631727
2018 TANGO1, cTAGE5, and SEC12 (PREB) are co-packaged with procollagen I (PC1) into large COPII carriers during ER export. SEC12 is particularly enriched around ER membranes and large COPII carriers containing PC1, whereas it is excluded from small (<100 nm) COPII vesicles. A split-GFP reconstitution system targeting SEC12 to PC1 via the luminal domain of TANGO1 enriches SEC12 around PC1 and generates enlarged PC1 carriers, demonstrating that SEC12 co-packaging is causally required for generation of large COPII carriers for bulky cargo. Vesicle budding assay with cargo fractionation; split-GFP reconstitution system; fluorescence imaging of SEC12 distribution around COPII carriers; immunoblotting of carrier fractions Proceedings of the National Academy of Sciences of the United States of America High 30545919
2021 Under stress conditions, SEC12 (PREB) mediates formation of a novel ERGIC-ERES membrane contact by directly interacting with TMED9. This contact (as close as 2–5 nm) allows ERES-located SEC12 to transactivate COPII assembly on the ERGIC membrane, promoting formation of ERGIC-derived COPII vesicles that serve as autophagosome membrane precursors. A portion of SEC12 also relocates to the ERGIC. This ERGIC-ERES contact is physically and functionally distinct from the TFG-mediated ERGIC-ERES adjunction involved in secretory transport. Co-immunoprecipitation (TMED9–SEC12 interaction); electron microscopy measuring inter-membrane distance; siRNA knockdown with autophagosome biogenesis readout; COPII assembly assay on ERGIC; fluorescence imaging of SEC12 relocalization Cell research High 34561617

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 2890 3262202
1984 Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proceedings of the National Academy of Sciences of the United States of America 888 6438633
1993 SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER. Nature 397 8377826
1982 Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development. Immunological reviews 381 6984001
2013 Orchestrating B cell lymphopoiesis through interplay of IL-7 receptor and pre-B cell receptor signalling. Nature reviews. Immunology 255 24378843
2008 Pre-B cell colony-enhancing factor (PBEF)/visfatin: a novel mediator of innate immunity. Journal of leukocyte biology 232 18252866
1984 Pre-B cell leukemia associated with chromosome translocation 1;19. Blood 194 6607758
1994 Bruton tyrosine kinase is tyrosine phosphorylated and activated in pre-B lymphocytes and receptor-ligated B cells. Proceedings of the National Academy of Sciences of the United States of America 179 7524098
2010 The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development. Science signaling 166 20699475
2006 CD24 affects CXCR4 function in pre-B lymphocytes and breast carcinoma cells. Journal of cell science 151 16390867
1996 Identification of stromal cell products that interact with pre-B cells. The Journal of cell biology 150 8707854
2012 Crosstalk between ROR1 and the Pre-B cell receptor promotes survival of t(1;19) acute lymphoblastic leukemia. Cancer cell 140 23153538
2001 Novel NEMO/IkappaB kinase and NF-kappa B target genes at the pre-B to immature B cell transition. The Journal of biological chemistry 134 11279141
2008 Erk kinases link pre-B cell receptor signaling to transcriptional events required for early B cell expansion. Immunity 132 18356083
2003 The nonimmunoglobulin portion of lambda5 mediates cell-autonomous pre-B cell receptor signaling. Nature immunology 126 12897780
1992 Fission yeast and a plant have functional homologues of the Sar1 and Sec12 proteins involved in ER to Golgi traffic in budding yeast. The EMBO journal 106 1396601
2008 Censoring of autoreactive B cell development by the pre-B cell receptor. Science (New York, N.Y.) 103 18566249
2013 BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint. Nature medicine 101 23852341
2016 PTEN opposes negative selection and enables oncogenic transformation of pre-B cells. Nature medicine 100 26974310
2001 Differential effects of p19(Arf) and p16(Ink4a) loss on senescence of murine bone marrow-derived preB cells and macrophages. Proceedings of the National Academy of Sciences of the United States of America 96 11481442
2015 C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis. Stem cell reports 90 26235892
2014 Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia. Proceedings of the National Academy of Sciences of the United States of America 88 24821775
2014 Concentration of Sec12 at ER exit sites via interaction with cTAGE5 is required for collagen export. The Journal of cell biology 88 25202031
1981 Pre-B cells; normal and abnormal development. Journal of clinical immunology 86 6801081
2007 Structural insight into pre-B cell receptor function. Science (New York, N.Y.) 84 17431183
1988 Structure and pre-B lymphocyte restricted expression of the VpreB in humans and conservation of its structure in other mammalian species. The EMBO journal 84 3258819
2013 Ikaros is absolutely required for pre-B cell differentiation by attenuating IL-7 signals. The Journal of experimental medicine 81 24297995
2013 Pre-B cell colony enhancing factor (PBEF), a cytokine with multiple physiological functions. Cytokine & growth factor reviews 71 23787158
2002 Multiple hematopoietic cell lineages develop in vivo from transplanted Pax5-deficient pre-B I-cell clones. Blood 70 11781227
2021 A new type of ERGIC-ERES membrane contact mediated by TMED9 and SEC12 is required for autophagosome biogenesis. Cell research 69 34561617
2006 Clustering of pre-B cell integrins induces galectin-1-dependent pre-B cell receptor relocalization and activation. Journal of immunology (Baltimore, Md. : 1950) 68 16818733
1982 Microenvironmental studies of pre-B and B cell development in human and mouse fetuses. Journal of immunology (Baltimore, Md. : 1950) 67 6806373
2005 Mimicry of a constitutively active pre-B cell receptor in acute lymphoblastic leukemia cells. The Journal of experimental medicine 66 15939795
1987 A pre-B cell nuclear protein that specifically interacts with the immunoglobulin V-J recombination sequences. Cell 62 3500792
1999 The inactive form of a yeast casein kinase I suppresses the secretory defect of the sec12 mutant. Implication of negative regulation by the Hrr25 kinase in the vesicle budding from the endoplasmic reticulum. The Journal of biological chemistry 61 9920934
1992 A pre-B- and B cell-specific DNA-binding protein, EBB-1, which binds to the promoter of the VpreB1 gene. European journal of immunology 60 1730258
2003 Role of apical caspases and glucocorticoid-regulated genes in glucocorticoid-induced apoptosis of pre-B leukemic cells. Cancer research 59 12517795
2003 Mimicry of pre-B cell receptor signaling by activation of the tyrosine kinase Blk. The Journal of experimental medicine 59 14662906
2014 Interleukin-15 enhances cellular proliferation and upregulates CNS homing molecules in pre-B acute lymphoblastic leukemia. Blood 57 24700781
2010 The pre-B cell receptor checkpoint. FEBS letters 57 20420836
2006 KLF4 suppresses transformation of pre-B cells by ABL oncogenes. Blood 57 16954505
2001 The absence of SLP65 and Btk blocks B cell development at the preB cell receptor-positive stage. European journal of immunology 53 11449370
2011 Pre-B cell receptor-mediated activation of BCL6 induces pre-B cell quiescence through transcriptional repression of MYC. Blood 52 21856866
1985 Pre-B cells in peripheral blood of multiple myeloma patients. Blood 52 3893567
2006 BCR-ABL1 induces aberrant splicing of IKAROS and lineage infidelity in pre-B lymphoblastic leukemia cells. Oncogene 51 16205638
2002 The transient expression of pre-B cell receptors governs B cell development. Seminars in immunology 51 12220935
2018 The Role of the Pre-B Cell Receptor in B Cell Development, Repertoire Selection, and Tolerance. Frontiers in immunology 50 30498490
1983 Isotype switching in murine pre-B cell lines. Cell 50 6311431
2009 Genome-wide analysis of the PreA/PreB (QseB/QseC) regulon of Salmonella enterica serovar Typhimurium. BMC microbiology 49 19236707
2012 Sec12 binds to Sec16 at transitional ER sites. PloS one 48 22347445
2012 Structural basis for galectin-1-dependent pre-B cell receptor (pre-BCR) activation. The Journal of biological chemistry 47 23124203
2001 Surrogate light chain-mediated interaction of a soluble pre-B cell receptor with adherent cell lines. Journal of immunology (Baltimore, Md. : 1950) 47 11714806
2019 Inhibition of the deubiquitinase USP9x induces pre-B cell homeobox 1 (PBX1) degradation and thereby stimulates prostate cancer cell apoptosis. The Journal of biological chemistry 46 30718275
2017 The BTG2-PRMT1 module limits pre-B cell expansion by regulating the CDK4-Cyclin-D3 complex. Nature immunology 46 28628091
2014 Pre-B cell receptor signaling induces immunoglobulin κ locus accessibility by functional redistribution of enhancer-mediated chromatin interactions. PLoS biology 45 24558349
2011 RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia. Blood 45 21606482
2003 The fission yeast spo14+ gene encoding a functional homologue of budding yeast Sec12 is required for the development of forespore membranes. Molecular biology of the cell 45 12631727
2002 The pre-B cell receptor and its role in proliferation and Ig heavy chain allelic exclusion. Seminars in immunology 45 12220934
2002 Cooperation between IL-7 and the pre-B cell receptor: a key to B cell selection. Seminars in immunology 45 12457615
2000 Pre-B and pre-T-cell receptors: conservation of strategies in regulating early lymphocyte development. Immunological reviews 44 10933593
2000 The bioflavonoid galangin blocks aryl hydrocarbon receptor activation and polycyclic aromatic hydrocarbon-induced pre-B cell apoptosis. Molecular pharmacology 44 10953044
2011 RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation. The Journal of experimental medicine 43 22201128
1993 Structure, biosynthesis, and transduction properties of the human mu-psi L complex: similar behavior of preB and intermediate preB-B cells in transducing ability. International immunology 43 8318451
1987 T-cell receptor and immunoglobulin genes are rearranged together in Abelson virus-transformed pre-B and pre-T cells. Molecular and cellular biology 43 2436035
2018 TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers. Proceedings of the National Academy of Sciences of the United States of America 42 30545919
2008 Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells. Blood 42 18385452
1999 Expression cloning and characterization of PREB (prolactin regulatory element binding), a novel WD motif DNA-binding protein with a capacity to regulate prolactin promoter activity. Molecular endocrinology (Baltimore, Md.) 42 10194769
2022 Single-cell analyses reveal early thymic progenitors and pre-B cells in zebrafish. The Journal of experimental medicine 41 35938989
2016 RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signals. The Journal of experimental medicine 41 26834154
2009 The epigenetic profile of Ig genes is dynamically regulated during B cell differentiation and is modulated by pre-B cell receptor signaling. Journal of immunology (Baltimore, Md. : 1950) 41 19155482
2004 The transitional ER localization mechanism of Pichia pastoris Sec12. Developmental cell 41 15130490
2017 Zebrafish B Cell Development without a Pre-B Cell Stage, Revealed by CD79 Fluorescence Reporter Transgenes. Journal of immunology (Baltimore, Md. : 1950) 40 28739882
1999 The roles of preB and B cell receptors in the stepwise allelic exclusion of mouse IgH and L chain gene loci. Seminars in immunology 40 10497085
1993 Rearrangement and expression of kappa light chain genes can occur without mu heavy chain expression during differentiation of pre-B cells. International immunology 40 8312230
1983 Immunoglobulin heavy-chain switching in pre-B leukaemias. Nature 38 6185849
2012 A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia. Epigenetics 37 22531296
2017 Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre-B ALL. The Journal of experimental medicine 35 28190001
2005 Initiation of pre-B cell receptor signaling: common and distinctive features in human and mouse. Seminars in immunology 33 16337808
1996 The VDJ repertoire expressed in human preB cells reflects the selection of bona fide heavy chains. European journal of immunology 33 8566085
1989 T cell receptor DJ but not VDJ rearrangement within a recombination substrate introduced into a pre-B cell line. International immunology 32 2562155
2013 BACH2-BCL6 balance regulates selection at the pre-B cell receptor checkpoint. Trends in immunology 31 24332591
2011 Pre-B cell to macrophage transdifferentiation without significant promoter DNA methylation changes. Nucleic acids research 31 22086955
2004 Mutational and expression analysis of the chromosome 12p candidate tumor suppressor genes in pre-B acute lymphoblastic leukemia. Leukemia 31 15284860
1999 Regulation of preB cell apoptosis by aryl hydrocarbon receptor/transcription factor-expressing stromal/adherent cells. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 31 10404042
2020 Increased O-GlcNAcylation of c-Myc Promotes Pre-B Cell Proliferation. Cells 29 31936366
2017 The miR-15 family reinforces the transition from proliferation to differentiation in pre-B cells. EMBO reports 29 28705801
2006 Role of Salmonella enterica serovar Typhimurium two-component system PreA/PreB in modulating PmrA-regulated gene transcription. Journal of bacteriology 29 16352830
2003 TEL-AML1 fusion precedes differentiation to pre-B cells in childhood acute lymphoblastic leukemia. Leukemia research 29 12526921
2002 The pre-B cell receptor signaling for apoptosis is negatively regulated by Fc gamma RIIB. Journal of immunology (Baltimore, Md. : 1950) 29 11777955
2002 The human V-preB promoter is a target for coordinated activation by early B cell factor and E47. Journal of immunology (Baltimore, Md. : 1950) 29 11994467
2014 KLF2--a negative regulator of pre-B cell clonal expansion and B cell activation. PloS one 28 24874925
2012 The structure of Sec12 implicates potassium ion coordination in Sar1 activation. The Journal of biological chemistry 28 23109340
2007 High expression of connective tissue growth factor in pre-B acute lymphoblastic leukaemia. British journal of haematology 28 17760805
1992 Protein-tyrosine phosphatase expression in pre-B cell NALM-6. Cancer research 28 1370651
2016 The DNA Damage Response Regulates RAG1/2 Expression in Pre-B Cells through ATM-FOXO1 Signaling. Journal of immunology (Baltimore, Md. : 1950) 27 27559048
2004 The pre-B cell receptor and its function during B cell development. Cellular & molecular immunology 27 16212894
1996 The immunosuppressant 15-deoxyspergualin [correction of 1,5-deoxyspergualin] reveals commonality between preT and preB cell differentiation. The Journal of experimental medicine 26 8676063
2020 The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution. Scientific reports 24 33154494
2015 NF-κB and AKT signaling prevent DNA damage in transformed pre-B cells by suppressing RAG1/2 expression and activity. Blood 23 26153519
2010 Cytogenetics in pre-B and B-cell acute lymphoblastic leukemia: a study of 208 patients diagnosed between 1981 and 2008. Cancer genetics and cytogenetics 23 20513528

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