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Showing BRINP1 — DBC1 is a alias.

BRINP1

BMP/retinoic acid-inducible neural-specific protein 1 · UniProt O60477

Length
761 aa
Mass
88.8 kDa
Annotated
2026-06-09
11 papers in source corpus 7 papers cited in narrative 7 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BRINP1 (DBCCR1/FAM5A) is a neural-enriched negative regulator of cell cycle progression that operates both in tumour suppression and in the control of neuronal production during brain development (PMID:11420708, PMID:24528488). In tumour cells, exogenous BRINP1 restrains proliferation by increasing the fraction of cells held in G1 phase (PMID:11420708), and is silenced in bladder cancer through CpG island promoter hypermethylation, with expression restorable by demethylating agents (PMID:9545632). Beyond growth arrest, re-expressed BRINP1 can trigger a non-classical, caspase-3-independent and TUNEL-negative form of cell death accompanied by redistribution of the protein from a diffuse cytoplasmic, nuclear-excluded pattern to granular cytoplasmic structures as cells round up and detach (PMID:14712213). In vivo, genetic ablation of BRINP1 in mice increases neurogenesis in the dentate gyrus subgranular zone, yielding a more immature granule cell population, consistent with its role as a suppressor of neural stem cell cycle progression (PMID:24528488). BRINP1 loss also disrupts cortical and hippocampal GABAergic interneuron populations, reducing parvalbumin- and somatostatin-expressing interneurons in the prefrontal cortex and altering neuronal migration gene expression (Astn1/Astn2) (PMID:27042284, PMID:29960053). The biochemical activity by which BRINP1 imposes G1 arrest and the molecular basis of its granular redistribution and cell death have not been characterized in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 1998 Medium

    Establishing why BRINP1/DBCCR1 expression is lost in cancer: the gene is epigenetically silenced rather than mutated, marking it as a candidate tumour suppressor.

    Evidence CpG island methylation analysis and demethylating-agent rescue in bladder cancer cell lines

    PMID:9545632

    Open questions at the time
    • Does not establish the functional consequence of silencing
    • No demonstration that re-expression alters tumour phenotype at this stage
  2. 2001 Medium

    Defining the cellular function behind tumour suppression: BRINP1 acts on the cell cycle, arresting cells in G1 rather than inducing death.

    Evidence Transient and stable transfection of DBCCR1 in NIH3T3 and bladder tumour cells with flow-cytometry cell-cycle analysis

    PMID:11420708

    Open questions at the time
    • No molecular mechanism for G1 arrest identified
    • No interacting cell-cycle machinery defined
  3. 2004 Medium

    Characterizing an additional fate imposed by BRINP1 re-expression: a non-classical cell death distinct from canonical apoptosis, linked to protein redistribution.

    Evidence DBCCR1-EGFP live-cell imaging, caspase-3 assay, and TUNEL staining in bladder tumour cells

    PMID:14712213

    Open questions at the time
    • The identity and composition of the granular structures are unknown
    • Death pathway not molecularly defined
    • Apparent discrepancy with the earlier non-apoptotic G1-arrest phenotype not reconciled
  4. 2014 Medium

    Extending BRINP1's cell-cycle role from tumour cells to physiology: it suppresses neural stem cell proliferation in vivo and shapes interneuron populations.

    Evidence BRINP1 knockout mouse with immunohistochemistry for neurogenesis and parvalbumin markers and behavioural phenotyping

    PMID:24528488

    Open questions at the time
    • Molecular pathway linking BRINP1 loss to increased neurogenesis unknown
    • Whether interneuron changes are cell-autonomous not established
  5. 2016 Medium

    Linking BRINP1 to neuronal positioning: its loss alters cortical interneuron density and migration-gene expression, implicating it in developmental neuronal distribution.

    Evidence Cre-mediated Brinp1 knockout with immunohistochemistry and Astn1/Astn2 expression analysis

    PMID:27042284

    Open questions at the time
    • Mechanistic connection between BRINP1 and Astn1/Astn2 regulation unresolved
    • Direct vs indirect effect on migration not distinguished
  6. 2017 Low

    Generalizing tumour suppression beyond bladder and probing a feedback loop: BRINP1 limits growth/migration/invasion in lung cancer and dampens DNMT1.

    Evidence siRNA knockdown and overexpression with proliferation/migration/invasion assays and DNMT1 expression analysis in lung cancer cells

    PMID:28427182

    Open questions at the time
    • Mechanism of DNMT1 attenuation not defined and not independently confirmed
    • Reciprocal methylation regulation remains correlative
  7. 2018 Medium

    Refining the regional specificity of BRINP1's developmental role: it is required for normal parvalbumin and somatostatin interneuron numbers in the prefrontal cortex.

    Evidence Quantitative immunohistochemistry in BRINP1-KO versus wild-type mouse medial prefrontal cortex

    PMID:29960053

    Open questions at the time
    • Does not establish whether interneuron loss reflects altered production, migration, or survival
    • Molecular effector remains unidentified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The biochemical activity of BRINP1 remains undefined: how it imposes G1 arrest, what molecular partners mediate its action, and the mechanism of its granular redistribution and caspase-independent death are unknown.
  • No enzymatic activity or direct binding partner identified
  • No structural model
  • Mechanism connecting cytoplasmic localization to cell-cycle and death control unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Localization
GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 2

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 DBCCR1 (BRINP1) is silenced in bladder cancer cell lines via CpG island hypermethylation at its 5' region, as demonstrated by methylation analysis and de novo expression induction by a demethylating agent. Methylation analysis of CpG island; treatment with demethylating agent restoring expression Genomics Medium 9545632
2001 Exogenous expression of DBCCR1 (BRINP1) in NIH3T3 cells and human bladder tumour cell lines suppresses proliferation by increasing the proportion of cells in G1 phase of the cell cycle, without altering apoptosis levels. Gene transfer (transient and stable transfection), cell cycle analysis by flow cytometry Oncogene Medium 11420708
2004 DBCCR1 (BRINP1) protein expressed as an EGFP fusion in bladder tumour cells initially showed diffuse cytoplasmic localisation with nuclear exclusion, then redistributed to granular cytoplasmic structures coinciding with cell rounding and detachment. This DBCCR1-mediated cell death was independent of caspase-3 activation and did not produce detectable DNA strand breaks (TUNEL-negative), indicating a non-classical apoptotic mechanism. Transient transfection with DBCCR1-EGFP fusion; live-cell fluorescence imaging; caspase-3 assay; TUNEL staining Oncogene Medium 14712213
2014 Genetic ablation of BRINP1 in mice increases neurogenesis in the subgranular zone of the dentate gyrus, producing a more immature neuronal population in the granule cell layer, and increases the number of parvalbumin-expressing interneurons in hippocampal CA1, establishing BRINP1 as a suppressor of cell cycle progression in neural stem cells in vivo. BRINP1 knockout (KO) mouse generation; immunohistochemistry for neurogenesis markers and parvalbumin; behavioural phenotyping Molecular brain Medium 24528488
2016 Knockout of Brinp1 in mice increases the density of parvalbumin-expressing interneurons in the adult neocortex and alters expression of neuronal migration genes Astn1 and Astn2, indicating that BRINP1 influences cortical neuronal distribution during development. Cre-mediated Brinp1 knockout; immunohistochemistry; expression analysis of Astn1/Astn2 Molecular autism Medium 27042284
2017 Restoration of DBCCR1 (BRINP1) expression in lung cancer cells inhibits growth, migration and invasion, while knockdown enhances these capacities. Additionally, DBCCR1 attenuates the expression of DNMT1, suggesting reciprocal regulation between DBCCR1 and DNA methylation machinery. siRNA knockdown; overexpression; proliferation, migration and invasion assays; DNMT1 expression analysis Oncotarget Low 28427182
2018 BRINP1-KO mice show a ~50% reduction in parvalbumin-expressing neurons and ~20% reduction in somatostatin-expressing neurons in the medial prefrontal cortex, indicating that BRINP1 is required for normal GABAergic interneuron populations in the mPFC. Immunohistochemistry in BRINP1-KO vs wild-type mice Neuroscience letters Medium 29960053

Source papers

Stage 0 corpus · 11 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Structure and methylation-based silencing of a gene (DBCCR1) within a candidate bladder cancer tumor suppressor region at 9q32-q33. Genomics 118 9545632
2001 Negative regulation of G(1)/S transition by the candidate bladder tumour suppressor gene DBCCR1. Oncogene 50 11420708
2016 Long non-coding RNA DBCCR1-003 regulate the expression of DBCCR1 via DNMT1 in bladder cancer. Cancer cell international 45 27777512
2014 Absence of BRINP1 in mice causes increase of hippocampal neurogenesis and behavioral alterations relevant to human psychiatric disorders. Molecular brain 39 24528488
2016 Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density. Molecular autism 36 27042284
2004 DBCCR1 mediates death in cultured bladder tumor cells. Oncogene 28 14712213
2004 Loss of heterozygosity at 9q33 and hypermethylation of the DBCCR1 gene in oral squamous cell carcinoma. British journal of cancer 22 15226771
2018 Decreased parvalbumin and somatostatin neurons in medial prefrontal cortex in BRINP1-KO mice. Neuroscience letters 17 29960053
2005 Low expression but infrequent genomic loss of the putative tumour suppressor DBCCR1 in astrocytoma. Oncology reports 13 15643521
2021 The conserved ASTN2/BRINP1 locus at 9q33.1-33.2 is associated with major psychiatric disorders in a large pedigree from Southern Spain. Scientific reports 7 34267256
2017 Identification of DBCCR1 as a suppressor in the development of lung cancer that is associated with increased DNA methyltransferase 1. Oncotarget 4 28427182

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