Affinage

BBC3

Bcl-2-binding component 3, isoforms 1/2 · UniProt Q9BXH1

Length
193 aa
Mass
20.5 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BBC3/PUMA is a BH3-only Bcl-2 family protein that serves as a central integrator of apoptotic death signals, transcriptionally induced as a direct p53 target that operates within a p53→PUMA→mitochondria→cytochrome c/Apaf-1 axis (PMID:11463392, PMID:11572983). Genetic ablation establishes PUMA as a critical mediator of both p53-dependent (DNA damage) and p53-independent (cytokine deprivation, glucocorticoids, staurosporine) apoptosis (PMID:14500851). Mechanistically, PUMA permeabilizes the mitochondrial outer membrane through dual activity: it de-represses pro-apoptotic effectors by binding anti-apoptotic Bcl-2 members and acts as a direct activator of BAX and BAK, binding the BAK BH3 groove with high affinity (KD ~26 nM) to drive homo-oligomerization and membrane permeabilization (PMID:19652530, PMID:24265320). In vivo, PUMA together with BIM and BID is essential for BAX/BAK activation, and PUMA alone is sufficient to activate BAX during cytokine deprivation (PMID:21127253, PMID:22015606). PUMA also couples nuclear and cytoplasmic p53 functions by displacing p53 from Bcl-xL, freeing cytoplasmic p53 to promote permeabilization (PMID:16151013). Beyond p53, the BBC3 promoter is transactivated by p73 (with Sp1), AP-1/c-Jun acting downstream of JNK1 and cooperating with CHOP, and FOXO transcription factors downstream of PI3K-AKT inhibition, and it is repressed by CTCF/Cohesin, HDAC3, Slug, and MYSM1-modulated p53 recruitment (PMID:14634023, PMID:19638343, PMID:20430872, PMID:20478995, PMID:23532334, PMID:26768662, PMID:18579560, PMID:22763818, PMID:24830722). PUMA stability is controlled by IKK-mediated Ser10 phosphorylation, which blocks chaperone-mediated autophagic degradation via HSC70 and promotes mitochondrial translocation (PMID:21997190, PMID:26212789), and PUMA induction is uniquely sensitive to glucose and growth-factor status (PMID:18990690, PMID:21159778). Functionally, PUMA mediates radiation-, chemotherapy-, and targeted-therapy-induced apoptosis of intestinal, hematopoietic, and germ-cell progenitors and contributes to developmental neuronal death (PMID:18522850, PMID:23532334, PMID:21762490, PMID:29795269). PUMA additionally amplifies necroptosis by triggering mitochondrial DNA release and activating STING/DAI sensors (PMID:29581256) and has non-apoptotic roles in autophagy and mitophagy (PMID:29229477, PMID:23122957, PMID:28277537).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    Established the existence and core function of PUMA as a mitochondrial BH3 protein linking p53 to the death machinery, answering whether a dedicated p53-induced apoptotic effector existed.

    Evidence Antisense inhibition, Bcl-2 co-IP, mitochondrial localization and cytochrome c release assays; promoter reporter with p53 binding sites and northern blot

    PMID:11463392 PMID:11572983

    Open questions at the time
    • Direct binding to BAX/BAK not yet shown
    • p53-independent inducers identified but mechanisms unresolved
  2. 2003 High

    Genetic loss-of-function defined PUMA as a non-redundant mediator of both p53-dependent and p53-independent apoptosis, settling whether PUMA was merely one of several redundant BH3 proteins.

    Evidence Puma knockout mice tested against DNA damage and multiple p53-independent insults; p73 transactivation of PUMA with Bax translocation in cells

    PMID:14500851 PMID:14634023

    Open questions at the time
    • Molecular mechanism of BAX/BAK activation not yet defined
    • Relative contribution of de-repression vs direct activation unknown
  3. 2005 High

    Revealed how PUMA bridges nuclear and cytoplasmic p53 pro-apoptotic functions, explaining how transcriptional p53 output licenses cytoplasmic p53 activity.

    Evidence Co-IP and Bcl-xL mutagenesis with genotoxic stress and mitochondrial permeabilization assays

    PMID:16151013

    Open questions at the time
    • Stoichiometry of the tripartite complex not defined
    • Generality across cell types untested
  4. 2008 Medium

    Defined tissue-level and transcriptional context for PUMA-driven progenitor apoptosis, addressing which cell populations depend on PUMA and which factors induce it under serum stress.

    Evidence Puma knockout mice with radiation and TUNEL in intestinal crypts; ChIP of Sp1 and p73 at PUMA promoter under serum starvation

    PMID:18522850 PMID:18579560

    Open questions at the time
    • Sp1/p73 cooperation mechanism is single-lab
    • Cross-tissue generality of intestinal findings limited
  5. 2009 Medium

    Mechanistically separated PUMA's de-repression and sensitization activities at the mitochondrion and identified JNK1/AP-1 as a stress-responsive transcriptional input.

    Evidence Reconstituted cell-free MOMP assay; ChIP, EMSA and dominant-negative c-Jun in Puma-/- hepatocytes

    PMID:19638343 PMID:19652530

    Open questions at the time
    • Direct-activator role for PUMA not yet quantified biochemically
    • AP-1 mechanism specific to lipoapoptosis context
  6. 2010 High

    Demonstrated by in vivo genetic epistasis that PUMA (with BIM and BID) is essential for BAX/BAK activation and dissected metabolic and chromatin-level control of PUMA expression.

    Evidence Bid/Bim/Puma triple-KO mice phenocopying Bax/Bak DKO; glucose deprivation in p53-/- and Puma-/- T cells; CTCF/Cohesin and HDAC3 ChIP with knockdown; CHOP:c-Jun co-IP

    PMID:18990690 PMID:20430872 PMID:20478995 PMID:21127253 PMID:21159778

    Open questions at the time
    • Whether PUMA acts as direct activator vs purely de-repressor still ambiguous from epistasis
    • Metabolic regulation of PUMA protein stability mechanism incomplete
  7. 2011 High

    Showed PUMA alone is sufficient to directly activate BAX, defined post-translational regulation by IKK, and established developmental and stem-cell-specific PUMA dependencies.

    Evidence Puma/Bim DKO mast cells with ABT-737; IKK1/2/NEMO Ser10 phospho-PUMA degradation; Bbc3-/- retinal cell counts; phosphomimetic p53 knock-in epistasis; 6-OHDA dopaminergic neuron KO

    PMID:20818388 PMID:21211034 PMID:21762490 PMID:21997190 PMID:22015606

    Open questions at the time
    • Direct vs indirect BAX activation distinction still debated in field
    • Ser10 phosphorylation degradation route (proteasome vs lysosome) not yet reconciled
  8. 2013 High

    Provided definitive biochemical proof that PUMA is a direct BAK activator and identified FOXO-mediated PUMA induction as the effector of targeted cancer therapies.

    Evidence Surface plasmon resonance (KD 26 nM), liposome/mitochondrial permeabilization with BH3 mutants; FOXO promoter activation with Puma/Bim-deficient tumor models; iPSC reprogramming in Puma-/- cells

    PMID:23532334 PMID:23873265 PMID:24265320

    Open questions at the time
    • Structural model of PUMA-BAK complex not resolved
    • In-cell contribution of direct activation vs de-repression still context-dependent
  9. 2014 Medium

    Extended PUMA's role to p53-independent drug-induced apoptosis via NF-κB and identified transcriptional repressors controlling PUMA in cancer.

    Evidence PUMA-null colorectal and other cancer cells with NF-κB pathway dissection and xenografts; Slug repression with rescue; HDAC3 ChIP and de-repression

    PMID:22763818 PMID:24563542 PMID:24763611 PMID:24830722

    Open questions at the time
    • Direct Slug binding to promoter not fully demonstrated
    • NF-κB-to-PUMA promoter link mechanistic detail incomplete
  10. 2015 Medium

    Resolved that PUMA is degraded by chaperone-mediated autophagy and that MCL-1's survival function in stem cells operates principally through PUMA inhibition.

    Evidence PUMA-HSC70 co-IP and lysosome fractionation with Ser10 mutants; Mcl-1+/-;Puma-/- hematopoietic epistasis

    PMID:25847014 PMID:26212789

    Open questions at the time
    • CMA contribution relative to proteasomal degradation not quantified
    • MCL-1/PUMA epistasis is single context
  11. 2016 High

    Defined chromatin-level antagonism of PUMA induction by MYSM1 and confirmed PUMA as the non-redundant p53 apoptotic effector in progenitors.

    Evidence MYSM1-p53 co-IP, histone-mark and p53-recruitment ChIP, Mysm1/Puma double-KO mice

    PMID:26768662

    Open questions at the time
    • Whether MYSM1 acts on other p53 targets equivalently unresolved
    • Direct enzymatic activity of MYSM1 at locus not detailed here
  12. 2017 Medium

    Uncovered non-apoptotic PUMA functions in autophagy and mitophagy through direct LC3 and p62 interactions.

    Evidence PUMA-LC3 and PUMA-p62 co-IP, ubiquitination and mitophagy assays; Bbc3 KO mice in silicosis with autophagy modulators

    PMID:28277537 PMID:29229477

    Open questions at the time
    • LIR-dependent function single-lab
    • Relationship between PUMA's apoptotic and autophagic roles unclear
  13. 2018 Medium

    Connected PUMA to necroptosis amplification via mitochondrial DNA release and cytosolic DNA sensing.

    Evidence RIP3/MLKL-KO and PUMA-deficient cells, mtDNA release assays, STING/DAI knockdown and RIP3/MLKL phosphorylation readouts

    PMID:29581256

    Open questions at the time
    • Mechanism of PUMA-induced mtDNA release not defined
    • In vivo relevance of necroptotic feedback loop untested
  14. 2020 High

    Established PUMA as the essential effector of chemotherapy-induced ovarian follicle loss, with agent-specific upstream control by TAp63.

    Evidence Puma-/- and TAp63-/- mice with follicle counting and fertility endpoints across cisplatin and cyclophosphamide

    PMID:29795269

    Open questions at the time
    • Upstream pathway for cyclophosphamide-induced PUMA induction unidentified
    • Translational relevance to human fertility preservation untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PUMA's apoptotic, necroptotic, autophagic/mitophagic, and pro-angiogenic activities are mechanistically partitioned and co-regulated within a single cell remains unresolved.
  • No structural model of PUMA-BAK/BAX complexes
  • Determinants selecting death vs autophagy outcome unknown
  • Integration of competing PTM/degradation routes unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060089 molecular transducer activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005739 mitochondrion 3 GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-9612973 Autophagy 3
Partners
BAK1BAXBCL2BCL2L1HSPA8MAP1LC3BMCL1SQSTM1

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 PUMA (BBC3) encodes two BH3 domain-containing proteins (PUMA-alpha and PUMA-beta) that bind Bcl-2, localize to the mitochondria to induce cytochrome c release, and activate programmed cell death. Antisense inhibition of PUMA reduced apoptotic response to p53, placing PUMA in the p53→PUMA→Bcl-2/mitochondria→cytochrome c/Apaf-1 pathway. Antisense inhibition, co-immunoprecipitation (Bcl-2 binding), mitochondrial localization assay, cytochrome c release assay, apoptosis assay Molecular cell High 11463392
2001 BBC3/bbc3 is a direct transcriptional target of p53, transactivated through consensus p53 binding sites within the bbc3 promoter. BBC3 mRNA is also induced by p53-independent stimuli (dexamethasone, serum deprivation) and suppressed by IGF-1 and EGF, indicating regulation by diverse survival signals. Promoter reporter assay, p53 binding site analysis, northern blot, growth factor stimulation/deprivation experiments Proceedings of the National Academy of Sciences of the United States of America High 11572983
2003 Puma deficiency in mice protects lymphocytes and fibroblasts from DNA damage-induced apoptosis and also protects cells from p53-independent cytotoxic insults (cytokine deprivation, glucocorticoids, staurosporine, phorbol ester), demonstrating Puma is a critical mediator of both p53-dependent and p53-independent apoptosis. Puma knockout mouse model, genetic epistasis, apoptosis assays in primary cells Science (New York, N.Y.) High 14500851
2005 PUMA couples nuclear and cytoplasmic p53 pro-apoptotic functions via a tripartite complex: Bcl-xL sequesters cytoplasmic p53; nuclear p53 induces PUMA expression; PUMA then displaces p53 from Bcl-xL, allowing cytoplasmic p53 to directly activate mitochondrial permeabilization. Mutant Bcl-xL that bound p53 but not PUMA rendered cells resistant to p53-induced apoptosis. Co-immunoprecipitation, mutagenesis of Bcl-xL, genotoxic stress experiments, mitochondrial permeabilization assay Science (New York, N.Y.) High 16151013
2003 p73 induces apoptosis by directly transactivating PUMA, which in turn causes Bax mitochondrial translocation and cytochrome c release. DeltaNp73 acts as a dominant negative inhibitor of this PUMA/Bax apoptotic pathway. Overexpression of p73 isoforms, PUMA promoter transactivation assay, Bax localization by immunofluorescence, cytochrome c release assay The Journal of biological chemistry Medium 14634023
2009 JNK1-dependent phosphorylation of c-Jun mediates PUMA induction during hepatocyte lipoapoptosis. The AP-1 complex containing phospho-c-Jun directly binds the PUMA promoter (confirmed by EMSA and ChIP). PUMA knockdown attenuates Bax activation, caspase 3/7 activity, and cell death. Dominant negative c-Jun, ChIP, EMSA, shRNA knockdown, primary murine hepatocytes from Puma-/- mice The Journal of biological chemistry High 19638343
2010 CHOP and AP-1 (c-Jun) cooperatively mediate PUMA induction during hepatocyte lipoapoptosis via a CHOP:phospho-c-Jun heteromeric complex that binds the AP-1 consensus sequence within the PUMA promoter; no functional CHOP binding sites were found directly in the PUMA promoter. shRNA knockdown of CHOP, co-immunoprecipitation of CHOP with c-Jun, ChIP assay American journal of physiology. Gastrointestinal and liver physiology Medium 20430872
2010 BID, BIM, and PUMA are essential for activation of BAX and BAK. Triple-knockout mice (Bid/Bim/Puma) phenocopy Bax/Bak double-knockout developmental defects (persistent interdigital webs, imperforate vaginas), and triple-KO cells fail to homo-oligomerize BAX/BAK or release cytochrome c in response to diverse death signals. Triple knockout mouse model, genetic epistasis, cross-linking/immunoblot for BAX/BAK oligomerization, cytochrome c release, caspase activation Science (New York, N.Y.) High 21127253
2009 PUMA promotes mitochondrial outer membrane permeabilization (MOMP) through two mechanisms: de-repression (binding anti-apoptotic Bcl-2 proteins to release BAX/BAK) and sensitization. Both mechanisms rely on PUMA binding to anti-apoptotic BCL-2 family members. PUMA cooperates with direct activator proteins (BIM, tBID) to efficiently induce MOMP. Reconstituted MOMP assay, protein-protein interaction studies, cell-free system Cell cycle (Georgetown, Tex.) Medium 19652530
2013 Puma BH3 domain binds Bak with high affinity (KD = 26 ± 5 nM) by surface plasmon resonance and directly induces Bak homo-oligomerization and membrane permeabilization of liposomes and mitochondria. Mutations that inhibit or enhance Puma BH3 binding to Bak produce corresponding changes in Bak oligomerization, membrane permeabilization, and Bak-mediated cell killing, establishing Puma as a direct Bak activator. Surface plasmon resonance, crosslinking/immunoblot for Bak oligomerization, liposome permeabilization assay, site-directed mutagenesis, cell viability assay The Journal of biological chemistry High 24265320
2011 Either Puma or Bim can directly activate Bax to cause mitochondrial outer membrane permeabilization. In Puma/Bim double-knockout primary mast cells, there is complete protection from cytokine starvation and DNA damage equivalent to Bax/Bak double KO. ABT-737 treatment of cytokine-deprived cells showed Puma alone is sufficient to activate Bax even without Bim, Bid, or p53. Double-knockout mouse models, ABT-737 BH3 mimetic treatment, cytochrome c release assay, mitochondrial membrane permeability assay Cell death and differentiation High 22015606
2011 CTCF and the Cohesin complex occupy intragenic chromatin boundaries of the PUMA locus and act as gene-specific repressors. CTCF knockdown leads to increased basal PUMA expression without p53 activation, mediated by changes in histone marks (H3K4me3, H3K9Ac, H3K9me3) at intragenic boundary regions. ChIP assay, CTCF knockdown (siRNA), histone modification analysis, RNA analyses Genes & development Medium 20478995
2011 IKK1/IKK2/NEMO kinase complex phosphorylates PUMA at serine 10 following serum or IL-3 stimulation. Serine 10 phosphorylation targets PUMA for proteasomal degradation, reducing its stability. Phosphorylated PUMA retains ability to co-immunoprecipitate with anti-apoptotic Bcl-2 family members but is rapidly degraded. Co-immunoprecipitation (IKK complex with PUMA), phospho-specific antibody, proteasome inhibitor experiments, IL-3 stimulation Cell death and differentiation Medium 21997190
2015 PUMA protein is a bona fide substrate of chaperone-mediated autophagy (CMA): PUMA associates with HSPA8/HSC70 leading to lysosomal translocation and degradation. IKKβ-mediated phosphorylation of PUMA at Ser10 stabilizes PUMA by blocking CMA-dependent degradation and facilitates PUMA translocation from cytosol to mitochondria, promoting TNF-induced apoptosis. Co-immunoprecipitation (PUMA-HSC70), lysosome fractionation, CMA inhibition, site-directed mutagenesis (Ser10), subcellular fractionation Autophagy Medium 26212789
2018 PUMA is transcriptionally activated in an RIP3/MLKL-dependent manner during necroptosis via autocrine TNF-α and NF-κB signaling. Induced PUMA promotes cytosolic release of mitochondrial DNA and activates DNA sensors DAI/ZBP1 and STING, leading to enhanced RIP3 and MLKL phosphorylation in a positive feedback loop that amplifies necroptotic death. RIP3/MLKL knockout cells, PUMA-deficient cells, mitochondrial DNA release assay, STING/DAI knockdown, RIP3/MLKL phosphorylation assay Proceedings of the National Academy of Sciences of the United States of America Medium 29581256
2008 PUMA mediates radiation-induced apoptosis in intestinal progenitor and stem cells in a p53-dependent manner through the mitochondrial pathway. PUMA-deficient mice show blocked apoptosis in intestinal crypt progenitor/stem cells, enhanced regeneration, and prolonged survival after lethal radiation doses. PUMA deficiency had little effect on radiation-induced intestinal endothelial apoptosis. Puma knockout mouse model, p53 dependence analysis, mitochondrial pathway assay, TUNEL staining, antisense oligonucleotide knockdown Cell stem cell High 18522850
2013 PUMA and BIM are key apoptotic effectors of tyrosine kinase inhibitors (TKIs) in HER2-amplified breast cancer and EGFR-mutant lung cancer. MEK-ERK pathway inhibition increases BIM abundance; PI3K-AKT pathway inhibition triggers FOXO transcription factor nuclear translocation to directly activate the PUMA promoter. Deficiency of Puma impairs TKI-induced tumor regression in vivo. Signal pathway inhibitors, FOXO nuclear translocation assay, PUMA promoter reporter, Puma/Bim-deficient mouse tumor models, caspase activation assay Science signaling High 23532334
2010 BBC3/Puma deficiency rescues adult stem cells from p53-dependent apoptosis in a constitutively active p53 knock-in mouse model (T21D/S23D), preventing depletion of stem cells in bone marrow, brain, and testes and rescuing segmental progeria. Puma knockout mice crossed with phosphomimetic p53 knock-in mice, stem cell enumeration, genetic epistasis Nature cell biology High 20818388
2016 MYSM1 protein associates with p53 and co-localizes to the BBC3/PUMA and CDKN1A/p21 promoters, antagonizing p53-driven expression by modulating local histone modifications (H3K27ac, H3K4me3) and p53 recruitment. PUMA (not p21) is the essential non-redundant effector of p53-induced multipotent progenitor apoptosis downstream of MYSM1 loss. Co-immunoprecipitation (MYSM1-p53), ChIP (histone marks, p53 recruitment), Mysm1/Puma double-knockout mice, transcriptome analysis Cell death and differentiation High 26768662
2008 Sp1 binding to the PUMA promoter increases upon serum starvation and is required for PUMA induction (Sp1 inhibition abrogates it). p73 is upregulated by serum starvation and mediates PUMA induction through the p53-binding sites in the PUMA promoter. Sp1 and p73β cooperatively activate PUMA transcription in a PI3K/AKT-inhibitable manner. ChIP (Sp1 binding), promoter inhibitor assays, p73 knockdown, PI3K/AKT inhibitors Carcinogenesis Medium 18579560
2014 HDAC3 binds the PUMA promoter and represses PUMA expression in gastric cancer cells. HDAC3 knockdown (but not other HDACs) upregulates PUMA expression, and HDAC3 inhibition by TSA promotes p53 interaction with the PUMA promoter, de-repressing PUMA. ChIP (HDAC3 binding to PUMA promoter), siRNA knockdown of individual HDACs, TSA treatment, promoter reporter assay Journal of molecular medicine (Berlin, Germany) Medium 22763818
2011 BBC3/PUMA (but not BIM or BID) is required for BAX-dependent developmental apoptosis of retinal ganglion cells, bipolar cells, and dopaminergic amacrine cells; Bbc3-deficient mice have increased numbers of the same cell types as Bax-deficient mice. BBC3 was not a primary factor in BAX-dependent axonal injury-induced neurodegeneration in adult retinal ganglion cells. Bbc3 knockout mouse, cell-type specific counting, genetic comparison with Bax-/-, Bim-/-, Bid-/- mice Molecular neurodegeneration Medium 21762490
2015 MCL-1 promotes hematopoietic stem/progenitor cell survival during stress by inhibiting PUMA. Mcl-1+/-;Puma-/- double mutant mice are completely protected from myeloablative challenge, identifying PUMA inhibition as the key mechanism of MCL-1's survival function in this context. Mcl-1 heterozygous and Puma knockout mouse models, hematopoietic recovery assays, bone marrow transplantation Blood Medium 25847014
2013 PUMA suppresses iPSC generation in a p53-dependent manner by promoting apoptosis (not cell cycle arrest). PUMA deficiency leads to better survival with reduced DNA damage and fewer chromosomal aberrations during reprogramming, distinguishing PUMA from p21 (which causes opposite chromosomal outcomes when deleted). Puma-/- and p21-/- mouse strains, iPSC reprogramming efficiency, DNA damage assays, chromosomal aberration analysis Nature communications Medium 23873265
2014 Slug (SNAI2) directly represses the Puma (Bbc3) gene, suppressing apoptosis in metastatic carcinoma cells. Slug knockdown increases Puma expression, and Puma inhibition by RNAi rescues lung colonization in Slug-knockdown cells, establishing a direct Slug→PUMA repression axis in tumor cell survival during metastasis. shRNA knockdown, ChIP (Slug binding to Puma promoter implied by direct repression), lung colonization assay, rescue experiments Cancer research Medium 24830722
2010 Puma is metabolically regulated downstream of p53: glucose deprivation or growth factor withdrawal induces Puma via p53 activation; maintained glucose uptake (via Glut1 overexpression) suppresses Puma induction, Bax activation, and cell death. Puma regulation involves combined p53-dependent transcription and control of Puma protein stability (degraded in nutrient-replete conditions). Glut1 overexpression, glucose deprivation, p53-/- and Puma-/- primary T lymphocytes, Bax activation assay, DNA fragmentation The Journal of biological chemistry Medium 18990690
2010 Akt-mediated glycolysis suppresses Puma expression; Puma is uniquely sensitive to metabolic status among pro-apoptotic Bcl-2 family members. Alternative mitochondrial fuels suppress Puma induction, indicating mitochondrial metabolites regulate Puma. Puma deficiency rescues cells from glucose deprivation-induced death, and Akt cannot readily block Puma-mediated apoptosis once Puma is expressed. Constitutively active Akt expression, glucose deprivation, Puma-/- cells, metabolic substrate supplementation, protein stability assays The Journal of biological chemistry Medium 21159778
2014 Regorafenib induces PUMA in colorectal cancer cells irrespective of p53 status through the NF-κB pathway following ERK inhibition and GSK3β activation. PUMA is necessary for regorafenib-induced apoptosis, antiangiogenic effects, and antitumor activity in vivo. PUMA-/- HCT116 cells, NF-κB pathway inhibition, xenograft tumor model, apoptosis assays Clinical cancer research Medium 24763611
2014 Aurora kinase inhibition induces PUMA via the canonical NF-κB pathway (p65) following AKT inhibition, independent of p53 status. PUMA is required for mitochondria-mediated apoptosis induced by aurora kinase inhibitors; PUMA deficiency increases polyploidy and improves cell survival. siRNA knockdown of aurora kinases, small molecule inhibitors, PUMA-/- cells, NF-κB p65 activation assays Molecular cancer therapeutics Medium 24563542
2017 BBC3/PUMA LC3-interacting region (LIR) at its C-terminal end interacts with LC3 to stimulate mitophagy. PUMA is also ubiquitinated and interacts with p62 to promote mitophagy, indicating PUMA-mediated mitophagy occurs in both p62-dependent and p62-independent manner. Co-immunoprecipitation (PUMA-LC3, PUMA-p62), gain and loss of function of PUMA, ubiquitination assay, mitophagy assay Biochimica et biophysica acta. Molecular cell research Medium 29229477
2006 PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53: PUMA cDNA transfection induces apoptosis equally in p53-deficient (siRNA-depleted or dominant-negative) human FLS and p53-/- murine FLS. p53 siRNA, dominant-negative p53, p53-/- murine FLS, PUMA cDNA transfection, caspase-3 activation, ELISA for histone release Arthritis research & therapy Medium 17014719
2012 PUMA has an unexpected pro-angiogenic function: Puma deficiency inhibits developmental and pathological angiogenesis and reduces microglia numbers in vivo. Mechanistically, PUMA regulates autophagy by modulating ERK activation and intracellular calcium levels in vascular/microglia cells. Puma knockout mice, shRNA knockdown, in vivo angiogenesis assays, ERK activation assay, calcium measurement Cell reports Medium 23122957
2017 BBC3/PUMA promotes autophagy in macrophages exposed to SiO2; knockdown of BBC3 decreases SiO2-induced autophagy, macrophage activation, and apoptosis. In Bbc3 knockout mice, decreased autophagy and reduced fibrosis progression were observed in silicosis models. BBC3 siRNA knockdown, autophagy inhibitor (3-MA), rapamycin, Bbc3 knockout mice, conditioned medium experiments Cell death & disease Medium 28277537
2006 Puma and Noxa differentially participate in p53-induced MOMP: In normal cells, Puma (but not Noxa) induces MOMP partly via calcium release from the ER and subsequent caspase activation. Upon E1A expression, cells become susceptible to MOMP induction by Noxa via an ER-independent pathway. Puma-/- and Noxa-/- cells, E1A expression, ER calcium release assay, MOMP measurement The EMBO journal Medium 17024184
2020 Loss of PUMA (BBC3) completely preserves primordial follicles following cyclophosphamide or cisplatin treatment in mice. TAp63 mediates PUMA-dependent oocyte apoptosis in response to cisplatin but not cyclophosphamide, indicating mechanistic differences between chemotherapy agents. Puma-/- and TAp63-/- mouse models, follicle counting, fertility testing, offspring health assessment Cell death & disease High 29795269
2011 6-OHDA-induced dopaminergic neuron death requires Puma and p53: p53 and DNA damage (not UPR/ATF3) mediate 6-OHDA-induced Puma upregulation and cell death. Puma-null primary midbrain cultures and mice show protection from 6-OHDA-induced death. Puma-/- mice, primary midbrain cultures, in vivo 6-OHDA injection, ATF3-/- comparison, DNA damage assays Molecular neurodegeneration Medium 21211034

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 PUMA, a novel proapoptotic gene, is induced by p53. Molecular cell 1916 11463392
2003 p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science (New York, N.Y.) 1090 14500851
2003 PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nature medicine 646 12563315
2008 PUMA, a potent killer with or without p53. Oncogene 467 19641508
2005 PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science (New York, N.Y.) 465 16151013
2010 BID, BIM, and PUMA are essential for activation of the BAX- and BAK-dependent cell death program. Science (New York, N.Y.) 392 21127253
2001 Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals. Proceedings of the National Academy of Sciences of the United States of America 375 11572983
2003 p73 Induces apoptosis via PUMA transactivation and Bax mitochondrial translocation. The Journal of biological chemistry 308 14634023
2005 GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. The Journal of clinical investigation 291 16322797
2010 MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Molecular cancer 264 20813046
2010 Palmitoleate attenuates palmitate-induced Bim and PUMA up-regulation and hepatocyte lipoapoptosis. Journal of hepatology 208 20206402
2008 PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell stem cell 181 18522850
2009 JNK1-dependent PUMA expression contributes to hepatocyte lipoapoptosis. The Journal of biological chemistry 166 19638343
2018 PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors. Proceedings of the National Academy of Sciences of the United States of America 161 29581256
2010 CHOP and AP-1 cooperatively mediate PUMA expression during lipoapoptosis. American journal of physiology. Gastrointestinal and liver physiology 155 20430872
2004 Suppression of tumorigenesis by the p53 target PUMA. Proceedings of the National Academy of Sciences of the United States of America 148 15192153
2006 The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target. Trends in pharmacological sciences 144 16766048
2008 Role of p53, PUMA, and Bax in wogonin-induced apoptosis in human cancer cells. Biochemical pharmacology 117 18377871
2012 PUMA, a critical mediator of cell death--one decade on from its discovery. Cellular & molecular biology letters 113 23001513
2018 Loss of PUMA protects the ovarian reserve during DNA-damaging chemotherapy and preserves fertility. Cell death & disease 106 29795269
2013 PUMA and BIM are required for oncogene inactivation-induced apoptosis. Science signaling 101 23532334
2013 Estrogen receptor β upregulates FOXO3a and causes induction of apoptosis through PUMA in prostate cancer. Oncogene 101 24077289
2008 Glucose metabolism attenuates p53 and Puma-dependent cell death upon growth factor deprivation. The Journal of biological chemistry 98 18990690
2014 Regorafenib inhibits colorectal tumor growth through PUMA-mediated apoptosis. Clinical cancer research : an official journal of the American Association for Cancer Research 92 24763611
2010 Puma is required for p53-induced depletion of adult stem cells. Nature cell biology 90 20818388
2009 PUMA cooperates with direct activator proteins to promote mitochondrial outer membrane permeabilization and apoptosis. Cell cycle (Georgetown, Tex.) 84 19652530
2006 PUMA sensitizes lung cancer cells to chemotherapeutic agents and irradiation. Clinical cancer research : an official journal of the American Association for Cancer Research 83 16675590
2006 Differential contribution of Puma and Noxa in dual regulation of p53-mediated apoptotic pathways. The EMBO journal 83 17024184
2010 Akt requires glucose metabolism to suppress puma expression and prevent apoptosis of leukemic T cells. The Journal of biological chemistry 82 21159778
2021 The role of P53 up-regulated modulator of apoptosis (PUMA) in ovarian development, cardiovascular and neurodegenerative diseases. Apoptosis : an international journal on programmed cell death 81 33783663
2021 Puma, noxa, p53, and p63 differentially mediate stress pathway induced apoptosis. Cell death & disease 79 34193827
2015 Targeting the miR-221-222/PUMA/BAK/BAX Pathway Abrogates Dexamethasone Resistance in Multiple Myeloma. Cancer research 79 26249174
2011 6-OHDA generated ROS induces DNA damage and p53- and PUMA-dependent cell death. Molecular neurodegeneration 78 21211034
2003 Zebrafish puma mutant decouples pigment pattern and somatic metamorphosis. Developmental biology 77 12679100
2011 p53 and PUMA independently regulate apoptosis of intestinal epithelial cells in patients and mice with colitis. Gastroenterology 76 21699775
2010 Gene-specific repression of the p53 target gene PUMA via intragenic CTCF-Cohesin binding. Genes & development 76 20478995
2017 BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis. Cell death & disease 73 28277537
2008 Sp1 and p73 activate PUMA following serum starvation. Carcinogenesis 73 18579560
2022 BH3-Only Proteins Noxa and Puma Are Key Regulators of Induced Apoptosis. Life (Basel, Switzerland) 68 35207544
2009 Expression and localization of GPR109A (PUMA-G/HM74A) mRNA and protein in mammalian retinal pigment epithelium. Molecular vision 65 19223991
2015 Chaperone-mediated autophagy prevents apoptosis by degrading BBC3/PUMA. Autophagy 61 26212789
2017 The role of ROS and subsequent DNA-damage response in PUMA-induced apoptosis of ovarian cancer cells. Oncotarget 57 28423586
2016 Repression of p53-target gene Bbc3/PUMA by MYSM1 is essential for the survival of hematopoietic multipotent progenitors and contributes to stem cell maintenance. Cell death and differentiation 55 26768662
2013 Evaluation of the BH3-only protein Puma as a direct Bak activator. The Journal of biological chemistry 55 24265320
2021 Fas/FasL mediates NF-κBp65/PUMA-modulated hepatocytes apoptosis via autophagy to drive liver fibrosis. Cell death & disease 52 33980818
2013 The p53-PUMA axis suppresses iPSC generation. Nature communications 51 23873265
2013 Hsp90 inhibitors promote p53-dependent apoptosis through PUMA and Bax. Molecular cancer therapeutics 48 23966620
2019 Long non-coding RNA CRNDE enhances cervical cancer progression by suppressing PUMA expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 44 31202167
2016 Mir143-BBC3 cascade reduces microglial survival via interplay between apoptosis and autophagy: Implications for methamphetamine-mediated neurotoxicity. Autophagy 44 27464000
2012 JNK- and Akt-mediated Puma expression in the apoptosis of cisplatin-resistant ovarian cancer cells. The Biochemical journal 44 22394200
2011 BBC3 (PUMA) regulates developmental apoptosis but not axonal injury induced death in the retina. Molecular neurodegeneration 44 21762490
2014 Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress. Reproductive sciences (Thousand Oaks, Calif.) 43 25425107
2014 Slug promotes survival during metastasis through suppression of Puma-mediated apoptosis. Cancer research 42 24830722
2009 PUMA suppresses intestinal tumorigenesis in mice. Cancer research 42 19491259
2006 The BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon cancer cells. Biochemical pharmacology 42 16595125
2017 PUMA dependent mitophagy by Abrus agglutinin contributes to apoptosis through ceramide generation. Biochimica et biophysica acta. Molecular cell research 41 29229477
2014 PUMA regulates germ cell loss and primordial follicle endowment in mice. Reproduction (Cambridge, England) 41 24859845
2024 Microneedle-assisted dual delivery of PUMA gene and celastrol for synergistic therapy of rheumatoid arthritis through restoring synovial homeostasis. Bioactive materials 38 38450203
2017 Proapoptotic PUMA targets stem-like breast cancer cells to suppress metastasis. The Journal of clinical investigation 38 29227280
2015 PUMA mediates the combinational therapy of 5-FU and NVP-BEZ235 in colon cancer. Oncotarget 38 25965911
2014 Degradation of Keap1 activates BH3-only proteins Bim and PUMA during hepatocyte lipoapoptosis. Cell death and differentiation 38 24769730
2015 p53/PUMA expression in human pulmonary fibroblasts mediates cell activation and migration in silicosis. Scientific reports 36 26576741
2014 β-Arrestin2 encourages inflammation-induced epithelial apoptosis through ER stress/PUMA in colitis. Mucosal immunology 36 25354317
2012 Histone deacetylase 3 inhibits expression of PUMA in gastric cancer cells. Journal of molecular medicine (Berlin, Germany) 36 22763818
2014 Aurora kinase inhibition induces PUMA via NF-κB to kill colon cancer cells. Molecular cancer therapeutics 34 24563542
2011 Genetically defining the mechanism of Puma- and Bim-induced apoptosis. Cell death and differentiation 34 22015606
2015 Antagonism between MCL-1 and PUMA governs stem/progenitor cell survival during hematopoietic recovery from stress. Blood 33 25847014
2015 Role of PUMA in methamphetamine-induced neuronal apoptosis. Toxicology letters 33 26524635
2018 miRNA‑222 promotes liver cancer cell proliferation, migration and invasion and inhibits apoptosis by targeting BBC3. International journal of molecular medicine 32 29693134
2017 PUMA gene delivery to synoviocytes reduces inflammation and degeneration of arthritic joints. Nature communications 31 28747638
2020 Copanlisib promotes growth inhibition and apoptosis by modulating the AKT/FoxO3a/PUMA axis in colorectal cancer. Cell death & disease 30 33139695
2019 Targeting mTOR suppressed colon cancer growth through 4EBP1/eIF4E/PUMA pathway. Cancer gene therapy 30 31257364
2014 miR-222 regulates the cell biological behavior of oral squamous cell carcinoma by targeting PUMA. Oncology reports 29 24452416
2011 Cytokine receptor signaling activates an IKK-dependent phosphorylation of PUMA to prevent cell death. Cell death and differentiation 29 21997190
2018 miR-663 sustains NSCLC by inhibiting mitochondrial outer membrane permeabilization (MOMP) through PUMA/BBC3 and BTG2. Cell death & disease 28 29352138
2013 PUMA Cooperates with p21 to Regulate Mammary Epithelial Morphogenesis and Epithelial-To-Mesenchymal Transition. PloS one 28 23805223
2024 Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3/PUMA pathway. Autophagy 27 39245438
2020 MiR-222-3p Promotes Cell Proliferation and Inhibits Apoptosis by Targeting PUMA (BBC3) in Non-Small Cell Lung Cancer. Technology in cancer research & treatment 27 32588752
2017 PUMA and NF-kB Are Cell Signaling Predictors of Reovirus Oncolysis of Breast Cancer. PloS one 27 28099441
2014 PUMA mediates ER stress-induced apoptosis in portal hypertensive gastropathy. Cell death & disease 27 24625987
2014 Caspase-9 mediates Puma activation in UCN-01-induced apoptosis. Cell death & disease 27 25356864
2014 MiR-222 targeted PUMA to improve sensitization of UM1 cells to cisplatin. International journal of molecular sciences 27 25474084
2009 Puma strikes Bax. The Journal of cell biology 27 19380876
2022 Synthetical lethality of Werner helicase and mismatch repair deficiency is mediated by p53 and PUMA in colon cancer. Proceedings of the National Academy of Sciences of the United States of America 26 36508676
2014 PUMA is invovled in ischemia/reperfusion-induced apoptosis of mouse cerebral astrocytes. Neuroscience 26 25451294
2012 Proliferative and survival effects of PUMA promote angiogenesis. Cell reports 26 23122957
2021 Porcine Epidemic Diarrhea Virus Induces Vero Cell Apoptosis via the p53-PUMA Signaling Pathway. Viruses 25 34202551
2007 TAT-RasGAP317-326 requires p53 and PUMA to sensitize tumor cells to genotoxins. Molecular cancer research : MCR 25 17510315
2015 MicroRNA-203 induces apoptosis by upregulating Puma expression in colon and lung cancer cells. International journal of oncology 24 26397233
2014 Interdependence of Bad and Puma during ionizing-radiation-induced apoptosis. PloS one 24 24516599
2014 Importance of proapoptotic protein PUMA in cell radioresistance. Folia biologica 24 24785107
2007 Ad-PUMA sensitizes drug-resistant choriocarcinoma cells to chemotherapeutic agents. Gynecologic oncology 24 17884151
2014 Evolution of puma lentivirus in bobcats (Lynx rufus) and mountain lions (Puma concolor) in North America. Journal of virology 23 24741092
2007 E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation. BMC cancer 23 17263886
2006 PUMA-mediated apoptosis in fibroblast-like synoviocytes does not require p53. Arthritis research & therapy 23 17014719
2020 PUMA: PANDA Using MicroRNA Associations. Bioinformatics (Oxford, England) 22 32860050
2017 Idelalisib induces PUMA-dependent apoptosis in colon cancer cells. Oncotarget 22 28008149
2020 PUMA-mediated epithelial cell apoptosis promotes Helicobacter pylori infection-mediated gastritis. Cell death & disease 21 32080167
2020 Inhibition of NOTCH signaling pathway chemosensitizes HCC CD133+ cells to vincristine and 5-fluorouracil through upregulation of BBC3. Biochemical and biophysical research communications 21 32173531
2020 Knockdown of circHomer1 ameliorates METH-induced neuronal injury through inhibiting Bbc3 expression. Neuroscience letters 21 32450188

Missed literature

Know a paper Affinage missed for BBC3? Flag it for the maintainers and the community.

No submissions yet.