Affinage

PHB1

Prohibitin 1 · UniProt P35232

Round 2 corrected
Length
272 aa
Mass
29.8 kDa
Annotated
2026-04-28
130 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PHB1 (prohibitin 1) is a multifunctional scaffold protein that assembles with PHB2 into large ring-shaped complexes (~12–14 copies each) at the mitochondrial inner membrane, where it chaperones newly synthesized mitochondrial translation products, stabilizes respiratory supercomplexes, maintains cristae architecture, and promotes mitophagy as an Atg8/LC3 receptor via a conserved LIR motif (PMID:11852914, PMID:28630166, PMID:38964378). PHB1 protein turnover is controlled by TRIM21-mediated ubiquitination, which is competitively blocked by LPLUNC1 or ERβ binding, and PHB1 loss leads to cytoplasmic mtDNA release that activates both NLRP3 inflammasome and cGAS-STING innate immune pathways (PMID:30886235, PMID:37359543, PMID:38820047). Outside mitochondria, PHB1 directly associates with the eIF4F translation initiation complex to regulate MYC mRNA translation, binds β-catenin to stabilize Wnt signaling, and interacts with C-RAF to sustain MEK-ERK pathway activation (PMID:37084385, PMID:37235908, PMID:31334335). The PHB complex is stabilized by SLP2/CHCHD10, and destabilization of this interaction—as caused by the ALS/FTD-linked CHCHD10 p.Ser59Leu mutation—triggers OMA1-dependent OPA1 processing, mitochondrial fragmentation, and motor neuron death (PMID:35656794).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2002 High

    Establishing the physical architecture and chaperone function of prohibitins resolved how PHB1 and PHB2 act at the mitochondrial inner membrane: they form a large multimeric ring complex that binds nascent mitochondrial translation products and shields them from AAA protease degradation.

    Evidence Biochemical fractionation, native molecular weight analysis, chaperone binding assays, and yeast genetics

    PMID:11852914

    Open questions at the time
    • No atomic-resolution structure of the ring complex
    • Substrate specificity of the chaperone holdase activity undefined
    • Mechanism of AAA protease exclusion unknown
  2. 2007 High

    Mapping the phosphorylation status of PHB1 (serine) and PHB2 (Tyr248) in human T cells and showing that knockdown collapses mitochondrial membrane potential established that post-translational modification of the PHB complex regulates mitochondrial integrity in immune cells.

    Evidence Subcellular fractionation, electron microscopy, mass spectrometry phosphosite mapping, site-directed mutagenesis, siRNA knockdown in human T cells

    PMID:18086671

    Open questions at the time
    • Kinase(s) responsible for PHB1 serine phosphorylation not identified
    • Functional consequence of individual phosphosites not dissected by phospho-dead mutants in vivo
  3. 2017 High

    Demonstrating that PHB complex deficiency impairs respiratory supercomplex assembly without reducing individual complex subunit levels pinpointed the PHB ring as a dedicated scaffold for supercomplex organization, linking it to elevated ROS production.

    Evidence PHB1/PHB2 siRNA, blue native PAGE for supercomplex assessment, mitoflash imaging, ROS measurement, rescue by PHB1+PHB2 co-expression

    PMID:28630166

    Open questions at the time
    • Mechanism by which PHB ring promotes supercomplex assembly is unclear
    • Whether PHB directly contacts respiratory complex subunits or acts via lipid remodeling is unresolved
  4. 2019 High

    Identification of TRIM21 as the E3 ubiquitin ligase targeting PHB1 for proteasomal degradation, and of LPLUNC1 as a competitive inhibitor of this ubiquitination, revealed the first regulated turnover mechanism for PHB1 protein levels.

    Evidence Reciprocal Co-IP, in vivo ubiquitination assays, competitive binding assays, NF-κB reporter rescue in nasopharyngeal carcinoma cells

    PMID:30886235

    Open questions at the time
    • Specific ubiquitinated lysine residues on PHB1 not mapped
    • Whether TRIM21-PHB1 axis operates in non-cancer cell types not shown
  5. 2019 Medium

    Showing that PHB1 physically interacts with C-RAF and sustains MEK-ERK phosphorylation downstream of FoxM1 transcriptional activation positioned PHB1 as a signaling scaffold in the RAS-MAPK pathway, with functional relevance to drug resistance.

    Evidence ChIP for FoxM1 binding to PHB1 promoter, Co-IP of PHB1–C-RAF, PHB1 knockdown/overexpression, paclitaxel resistance assays in pancreatic cancer

    PMID:31334335

    Open questions at the time
    • Structural basis of PHB1–C-RAF interaction unknown
    • Whether this interaction is direct or bridged by other partners not resolved
    • Single-lab observation
  6. 2021 Medium

    Independent confirmation that PHB1 activates RAF1-MEK-ERK signaling via direct interaction with STOML2 broadened the picture of PHB1 as a mitochondrial-to-cytoplasmic signaling node and identified a second mitochondrial partner (STOML2/SLP2) linking PHB1 to MAPK output.

    Evidence Yeast two-hybrid, reciprocal Co-IP, immunofluorescence co-localization, RAF inhibitor treatment in colorectal cancer cells and organoids

    PMID:34781982

    Open questions at the time
    • Whether PHB1–STOML2–RAF axis operates outside colorectal cancer is untested
    • Stoichiometry of the PHB1–STOML2 complex relative to the PHB ring unknown
  7. 2022 High

    Discovery that CHCHD10 and SLP2 cooperatively stabilize the PHB complex, and that the ALS/FTD mutation CHCHD10-S59L causes PHB–SLP2 aggregation triggering OMA1-OPA1 processing and motor neuron death, connected PHB complex integrity to neurodegenerative disease pathogenesis.

    Evidence Patient fibroblasts, Chchd10-S59L knock-in mouse, reciprocal Co-IP, electron microscopy of cristae, OMA1/OPA1 processing assays, spinal cord histology

    PMID:35656794

    Open questions at the time
    • Whether PHB stabilization rescues the CHCHD10-mutant phenotype not tested
    • Relevance to sporadic ALS unknown
  8. 2022 Medium

    Replication of TRIM21 as the PHB1 E3 ligase in a second biological context—where ERβ activation by arctigenin competitively disrupts TRIM21–PHB1 binding—validated the regulated ubiquitination mechanism and extended it to intestinal epithelial homeostasis.

    Evidence Co-IP, ubiquitination assays, ERβ knockdown in DSS-colitis mice, mucus barrier assessment

    PMID:35599350

    Open questions at the time
    • Whether ERβ binds the same PHB1 surface as TRIM21 not structurally resolved
    • Relative contributions of PHB1 stabilization versus other ERβ targets to mucosal protection unclear
  9. 2023 Medium

    Multiple studies converged on PHB1 as a guardian against innate immune activation: PHB1 loss increases cytoplasmic mtDNA that triggers NLRP3 inflammasome and cGAS-STING pathways, while PHB1 interaction with Sam50 at the outer membrane prevents mtDNA escape through mPTP and BAX pores.

    Evidence PHB1 siRNA, cytoplasmic mtDNA quantification, mitophagy inhibitor epistasis, Sam50 Co-IP, mPTP/BAX pore assays, mouse sepsis and renal models

    PMID:37359543 PMID:38820047

    Open questions at the time
    • Whether PHB1–Sam50 interaction is direct or mediated through the PHB ring is unclear
    • Relative contribution of mitophagy promotion versus mtDNA retention to immune suppression not separated
  10. 2023 High

    Demonstrating that PHB1 directly associates with the eIF4F translation initiation complex to regulate MYC mRNA translation—independently of RAS-RAF-MAPK—revealed a previously unsuspected cytoplasmic moonlighting function of PHB1 in cap-dependent translation control.

    Evidence Co-IP of PHB with eIF4F components, multiomics (transcriptomics, proteomics, translatomics), FL3 pharmacological inhibition and PHB knockdown in CLL cells, in vivo CLL mouse model

    PMID:37084385

    Open questions at the time
    • Structural basis of PHB1–eIF4F interaction unresolved
    • Whether this function operates in non-hematological cells unknown
    • Mechanism discriminating mRNA targets for PHB1-dependent translation not defined
  11. 2023 Medium

    Identification of PHB1 as a direct β-catenin-binding partner that stabilizes β-catenin by blocking its ubiquitin-mediated degradation added Wnt signaling activation to PHB1's extra-mitochondrial repertoire.

    Evidence Co-IP, PHB1 overexpression/knockdown, β-catenin rescue, nude mouse metastasis model in bladder cancer

    PMID:37235908

    Open questions at the time
    • Domain on PHB1 mediating β-catenin binding not mapped
    • Whether this interaction occurs in normal epithelial cells or is cancer-specific is unknown
  12. 2024 High

    Discovery that yeast Phb1/Phb2 function as bona fide Atg8 receptors via conserved AIM/LIR motifs, and that they negatively regulate Atg32 processing by the rhomboid protease Pcp1, established prohibitins as direct mediators—not merely permissive scaffolds—of mitophagy.

    Evidence Genetic deletion, Co-IP of Phb1/Phb2 with Atg8, AIM/LIR motif mutagenesis, mitophagy flux assays, Yme1/Pcp1 epistasis in S. cerevisiae

    PMID:38964378

    Open questions at the time
    • Conservation of the LIR-dependent mitophagy receptor function in mammalian PHB1 awaits direct demonstration
    • Relative importance of PHB1 versus canonical mitophagy receptors (BNIP3, FUNDC1) not compared

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the PHB1/PHB2 ring complex is lacking, the molecular logic by which PHB1 partitions between mitochondrial and cytoplasmic functions is unknown, and the identity of kinases phosphorylating PHB1 remains to be determined.
  • No cryo-EM or crystal structure of mammalian PHB ring
  • No mechanism explaining how PHB1 distributes between mitochondrial and cytoplasmic pools
  • Kinases for PHB1 serine phosphorylation unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0005198 structural molecule activity 3 GO:0044183 protein folding chaperone 1
Localization
GO:0005739 mitochondrion 6
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 2
Partners
CHCHD10CTNNB1PHB2RAF1SAM50STOML2TRIM21
Complex memberships
PHB1/PHB2 prohibitin ring complexeIF4F translation initiation complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 PHB1 (Phb1p) and PHB2 (Phb2p) form a large multimeric ring complex (~12–14 copies each) in the mitochondrial inner membrane that functions as a novel membrane-bound chaperone, binding directly to newly synthesized mitochondrial translation products and stabilizing them against degradation by membrane-bound AAA metalloproteases. Biochemical fractionation, native molecular weight analysis, chaperone binding assays, yeast genetic studies Cellular and molecular life sciences : CMLS High 11852914
2007 PHB1 and PHB2 localize to the mitochondrial inner membrane of human T cells (not the nucleus as previously reported), are serine-phosphorylated (PHB1) and serine/tyrosine-phosphorylated (PHB2, mapped to Tyr248 by MS and mutagenesis), and siRNA-mediated knockdown disrupts mitochondrial membrane potential, establishing that the PHB1/PHB2 phosphocomplex is required for mitochondrial integrity in T cells. Subcellular fractionation, immunofluorescence, electron microscopy, orthophosphate labeling, phosphoamino acid analysis, mass spectrometry, site-directed mutagenesis, phospho-specific antibodies, siRNA knockdown The Journal of biological chemistry High 18086671
2013 PHB (prohibitin 1) inhibits apoptosis in undifferentiated rat granulosa cells through a PHB → MEK-ERK1/2 → Bcl-2/Bcl-xL pathway: PHB overexpression increases anti-apoptotic Bcl-2 and Bcl-xL, reduces cytochrome c release, and inhibits caspase-3 activity, while PHB silencing causes mitochondrial fragmentation and sensitizes cells to apoptosis. Microarray, immunoblot, ectopic overexpression, siRNA knockdown, flow cytometry, mitochondrial morphology imaging Apoptosis : an international journal on programmed cell death Medium 24096434
2017 PHB complex deficiency impairs the formation of mitochondrial respiratory supercomplexes (RSCs) without altering the abundance of individual respiratory complex subunits, leading to elevated basal ROS production and increased mitochondrial flash (mitoflash) frequency up to 5.4-fold; the multimeric PHB1/PHB2 complex is the functional unit required for RSC assembly. PHB1/PHB2 siRNA knockdown, mitoflash imaging with fluorescent reporters, ROS measurement, blue native PAGE for RSC assessment, rescue by co-expression of PHB1 and PHB2 Journal of cell science High 28630166
2017 Japanese encephalitis virus (JEV) infection induces ER stress in human neural stem cells, and prohibitin (PHB/PHB1) interacts with JEV viral RNA, implicating PHB1 as a participant in ER stress-induced apoptosis during viral infection. 2D gel electrophoresis-based proteomics, mass spectrometry, in vivo validation in mice subventricular zone and human autopsy samples Cell death & disease Low 28102850
2019 LPLUNC1 stabilizes PHB1 protein by competitively blocking TRIM21-mediated ubiquitination of PHB1; LPLUNC1 binds PHB1 with higher affinity than TRIM21, preventing TRIM21 from ubiquitinating PHB1 and thus its proteasomal degradation. Stabilized PHB1 suppresses NF-κB activity in nasopharyngeal carcinoma cells, and PHB1 depletion reverses the anti-tumor effects of LPLUNC1. Co-immunoprecipitation, ubiquitination assays, competitive binding assays, siRNA knockdown, NF-κB reporter assays, rescue experiments Oncogene High 30886235
2019 FoxM1 transcription factor binds the PHB1 promoter and enhances PHB1 expression at transcriptional and post-transcriptional levels; PHB1 then interacts with C-RAF and promotes ERK1/2 phosphorylation, driving paclitaxel resistance in pancreatic cancer cells. PHB1 knockdown sensitizes resistant cells to paclitaxel, and ABCA2-mediated drug efflux also operates downstream of the FoxM1/PHB1/RAF-MEK-ERK axis. ChIP (chromatin immunoprecipitation), Co-immunoprecipitation, PHB1 knockdown/overexpression, in vitro and in vivo drug resistance assays, ERK1/2 phosphorylation immunoblot Molecular therapy oncolytics Medium 31334335
2020 HDAC6 downregulates PHB1 expression and function in sepsis; inhibition of HDAC6 restores PHB1-mediated mitochondrial respiratory chain function, reduces oxidant production, and protects against oxidative injury in a rat CLP sepsis model. qRT-PCR, western blotting, CLP sepsis model, HDAC6 inhibition, mitochondrial respiratory control rate measurement, histological analysis Aging Medium 32221047
2022 CHCHD10 (an ALS/FTD gene product) interacts with SLP2 (Stomatin-Like Protein 2) and together stabilize the PHB complex in the mitochondrial inner membrane; the CHCHD10 p.Ser59Leu mutation causes SLP2-prohibitin aggregates, destabilizes the PHB complex, activates the OMA1 cascade with OPA1 processing, leads to mitochondrial fragmentation and abnormal cristae morphogenesis, and results in motor neuron death in spinal cord. Patient fibroblasts, Chchd10S59L/+ mouse model, co-immunoprecipitation, immunofluorescence, electron microscopy, in vivo hippocampus and spinal cord histology, OMA1/OPA1 processing assays Brain : a journal of neurology High 35656794
2023 PHB1 knockdown increases cytoplasmic mtDNA levels and enhances NLRP3 inflammasome activation; mitophagy inhibitor treatment abolishes PHB1 knockdown-mediated NLRP3 activation, establishing that PHB1 suppresses NLRP3 inflammasome activation through promotion of mitophagy in the context of sepsis. PHB1 siRNA knockdown, cytoplasmic mtDNA quantification, NLRP3 inflammasome activation assays (IL-1β, caspase-1 cleavage), mitophagy inhibitor treatment, bioinformatic clustering of sepsis samples Frontiers in immunology Medium 37359543
2023 PHB1 physically interacts with Sam50 (mitochondrial outer membrane import channel) to stabilize mtDNA; lycopene reinforces this Sam50/PHB1 interaction to prevent mtDNA release into the cytoplasm via mPTP and BAX pores, thereby inhibiting cGAS-STING pathway activation and renal PANoptosis. Co-immunoprecipitation, mtDNA stability assays, mPTP/BAX pore measurements, cGAS-STING pathway readouts, mouse model (350 mice), lycopene treatment Journal of agricultural and food chemistry Medium 38820047
2023 PHB1 and PHB2 (prohibitins) are directly associated with the eIF4F translation initiation complex in chronic lymphocytic leukemia (CLL) cells; pharmacological targeting of PHBs with the flavagline FL3 or PHB knockdown inhibits translation of MYC oncogene mRNA and other oncogenic mRNAs, arrests proliferation, and rewires MYC-driven metabolism, with the RAS-RAF-MAPK pathway not involved in translation regulation in this context. Multiomics (transcriptomics, proteomics, translatomics), Co-immunoprecipitation of PHB with eIF4F components, FL3 treatment, PHB1/PHB2 siRNA knockdown, in vivo CLL mouse model, patient CLL sample analysis Blood High 37084385
2021 STOML2 interacts directly with PHB (prohibitin 1) as confirmed by co-immunoprecipitation and co-localization, and both proteins activate the MAPK signaling pathway (RAF1-MEK1/2-ERK1/2 phosphorylation) to promote colorectal cancer cell proliferation. Yeast two-hybrid screen, co-immunoprecipitation, immunofluorescence co-localization, STOML2 knockdown/overexpression, organoid culture, orthotopic model, RAF inhibitor (Sorafenib) treatment, immunoblotting for MAPK pathway Journal of experimental & clinical cancer research : CR Medium 34781982
2023 PHB1 binds β-catenin directly (confirmed by immunoprecipitation) and stabilizes it by inhibiting ubiquitin-mediated proteasomal degradation, thereby activating Wnt/β-catenin signaling to promote epithelial-mesenchymal transition (EMT), invasion, and metastasis in bladder cancer; β-catenin knockdown reverses PHB1 overexpression-driven cancer aggressiveness. Co-immunoprecipitation, immunofluorescence, PHB1 knockdown/overexpression, transwell/wound-healing assays, nude mouse lung metastasis model, western blotting for EMT and Wnt/β-catenin markers Pathology, research and practice Medium 37235908
2022 Arctigenin (phytoestrogen) activates estrogen receptor β (ERβ), which then competitively interacts with PHB1, disrupting TRIM21–PHB1 binding and blocking TRIM21-mediated ubiquitination of PHB1, thereby stabilizing PHB1 protein and inhibiting mitochondrial pathway-mediated apoptosis in intestinal goblet cells to preserve the mucus barrier in colitis. In vitro and in vivo IBD models, Co-immunoprecipitation, ubiquitination assays, ERβ knockdown in colonic tissue (DSS-colitis mice), western blotting Phytotherapy research : PTR Medium 35599350
2024 Yeast Phb1 (ortholog of human PHB1) and Phb2 function as novel Atg8 (LC3) receptors to sustain mitophagy in Saccharomyces cerevisiae: both contain a conserved AIM/LIR-like motif, physically interact and co-localize with Atg8 at mitochondria, and their complex formation is required for mitophagy. Additionally, prohibitins negatively regulate basal C-terminal processing of the mitophagy receptor Atg32 by the rhomboid protease Pcp1, with absence of prohibitins causing hyperactivated Atg32 processing. Genetic deletion of PHB1/PHB2, mitophagy flux assays, Co-immunoprecipitation of Phb1/Phb2 with Atg8, mitochondrial co-localization imaging, AIM/LIR motif mutagenesis, Yme1/Pcp1 epistasis analysis, Atg32 processing assays Autophagy High 38964378

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
2010 Network organization of the human autophagy system. Nature 1286 20562859
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2009 Genome-wide association study identifies eight loci associated with blood pressure. Nature genetics 956 19430483
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2002 Directed proteomic analysis of the human nucleolus. Current biology : CB 780 11790298
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2016 Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor. Cell 697 28017329
2012 A census of human soluble protein complexes. Cell 689 22939629
2015 Gene essentiality and synthetic lethality in haploid human cells. Science (New York, N.Y.) 657 26472760
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2013 Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nature genetics 463 23535732
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
1988 Cloning of the Alcaligenes eutrophus genes for synthesis of poly-beta-hydroxybutyric acid (PHB) and synthesis of PHB in Escherichia coli. Journal of bacteriology 295 2848014
2002 The mitochondrial PHB complex: roles in mitochondrial respiratory complex assembly, ageing and degenerative disease. Cellular and molecular life sciences : CMLS 252 11852914
2005 Flotillins and the PHB domain protein family: rafts, worms and anaesthetics. Traffic (Copenhagen, Denmark) 206 16101677
2020 Rational flux-tuning of Halomonas bluephagenesis for co-production of bioplastic PHB and ectoine. Nature communications 100 32620759
2001 Production of PHB by a Bacillus megaterium strain using sugarcane molasses and corn steep liquor as sole carbon and nitrogen sources. Microbiological research 95 11716209
2007 The PHB1/2 phosphocomplex is required for mitochondrial homeostasis and survival of human T cells. The Journal of biological chemistry 88 18086671
2005 Novel and economical purification of recombinant proteins: intein-mediated protein purification using in vivo polyhydroxybutyrate (PHB) matrix association. Protein science : a publication of the Protein Society 88 15883185
2021 Enhanced polyhydroxybutyrate (PHB) production by newly isolated rare actinomycetes Rhodococcus sp. strain BSRT1-1 using response surface methodology. Scientific reports 80 33479335
2011 Identification of a multifunctional protein, PhaM, that determines number, surface to volume ratio, subcellular localization and distribution to daughter cells of poly(3-hydroxybutyrate), PHB, granules in Ralstonia eutropha H16. Molecular microbiology 75 22023320
2017 Controlling cell volume for efficient PHB production by Halomonas. Metabolic engineering 74 28918285
2017 Overcoming STC2 mediated drug resistance through drug and gene co-delivery by PHB-PDMAEMA cationic polyester in liver cancer cells. Materials science & engineering. C, Materials for biological applications 69 29208281
2015 Characterization of poly-3-hydroxybutyrate (PHB) produced from Ralstonia eutropha using an alkali-pretreated biomass feedstock. International journal of biological macromolecules 68 26206741
2021 The protective role of PHB and its degradation products against stress situations in bacteria. FEMS microbiology reviews 67 33118006
1993 The human prohibitin (PHB) gene family and its somatic mutations in human tumors. Genomics 66 8244394
2018 Mitochondrial Quality Control Mechanisms and the PHB (Prohibitin) Complex. Cells 64 30501123
2009 PHB/PHBHHx scaffolds and human adipose-derived stem cells for cartilage tissue engineering. Biomaterials 64 19481254
2004 Unraveling the function of the Rhodospirillum rubrum activator of polyhydroxybutyrate (PHB) degradation: the activator is a PHB-granule-bound protein (phasin). Journal of bacteriology 61 15060050
2020 Metabolic engineering of Cupriavidus necator H16 for improved chemoautotrophic growth and PHB production under oxygen-limiting conditions. Metabolic engineering 58 32348842
2022 A Review on Enhancing Cupriavidus necator Fermentation for Poly(3-hydroxybutyrate) (PHB) Production From Low-Cost Carbon Sources. Frontiers in bioengineering and biotechnology 56 35928944
2017 Japanese encephalitis virus induces human neural stem/progenitor cell death by elevating GRP78, PHB and hnRNPC through ER stress. Cell death & disease 56 28102850
1996 Increased PHB productivity by high-cell-density fed-batch culture of Alcaligenes latus, a growth-associated PHB producer. Biotechnology and bioengineering 54 18626935
2018 Determination of Polyhydroxybutyrate (PHB) Content in Ralstonia eutropha Using Gas Chromatography and Nile Red Staining. Bio-protocol 53 34179275
2017 Deficiency of PHB complex impairs respiratory supercomplex formation and activates mitochondrial flashes. Journal of cell science 51 28630166
2007 The impact of PHB accumulation on L-glutamate production by recombinant Corynebacterium glutamicum. Journal of biotechnology 48 17555841
2007 Roles of poly-3-hydroxybutyrate (PHB) and glycogen in symbiosis of Sinorhizobium meliloti with Medicago sp. Microbiology (Reading, England) 47 17259610
2019 Systems-level engineering and characterisation of Clostridium autoethanogenum through heterologous production of poly-3-hydroxybutyrate (PHB). Metabolic engineering 46 30641139
2019 LPLUNC1 stabilises PHB1 by counteracting TRIM21-mediated ubiquitination to inhibit NF-κB activity in nasopharyngeal carcinoma. Oncogene 46 30886235
2016 Engineering the growth pattern and cell morphology for enhanced PHB production by Escherichia coli. Applied microbiology and biotechnology 45 27401924
2017 Engineering cell wall synthesis mechanism for enhanced PHB accumulation in E. coli. Metabolic engineering 44 29174524
2013 Prohibitin (PHB) inhibits apoptosis in rat granulosa cells (GCs) through the extracellular signal-regulated kinase 1/2 (ERK1/2) and the Bcl family of proteins. Apoptosis : an international journal on programmed cell death 44 24096434
2013 PhaM is the physiological activator of poly(3-hydroxybutyrate) (PHB) synthase (PhaC1) in Ralstonia eutropha. Applied and environmental microbiology 44 24212577
2017 Codelivery for Paclitaxel and Bcl-2 Conversion Gene by PHB-PDMAEMA Amphiphilic Cationic Copolymer for Effective Drug Resistant Cancer Therapy. Macromolecular bioscience 40 28714224
2014 A closer look on the polyhydroxybutyrate- (PHB-) negative phenotype of Ralstonia eutropha PHB-4. PloS one 40 24787649
2019 FoxM1 Induced Paclitaxel Resistance via Activation of the FoxM1/PHB1/RAF-MEK-ERK Pathway and Enhancement of the ABCA2 Transporter. Molecular therapy oncolytics 39 31334335
2014 Comparative proteome analysis reveals four novel polyhydroxybutyrate (PHB) granule-associated proteins in Ralstonia eutropha H16. Applied and environmental microbiology 39 25548058
2003 Poly(3-hydroxybutyrate) (PHB) synthesis by recombinant Escherichia coli harbouring Streptomyces aureofaciens PHB biosynthesis genes: effect of various carbon and nitrogen sources. Microbiological research 39 12608576
2020 On the Role and Production of Polyhydroxybutyrate (PHB) in the Cyanobacterium Synechocystis sp. PCC 6803. Life (Basel, Switzerland) 38 32331427
1997 Megaplasmid and chromosomal loci for the PHB degradation pathway in Rhizobium (Sinorhizobium) meliloti. Genetics 38 9258668
2018 Polyhydroxybutyrate (PHB) biodegradation using bacterial strains with demonstrated and predicted PHB depolymerase activity. Applied microbiology and biotechnology 37 29951858
2017 Microbial production, ultrasound-assisted extraction and characterization of biopolymer polyhydroxybutyrate (PHB) from terrestrial (P. hysterophorus) and aquatic (E. crassipes) invasive weeds. Bioresource technology 36 28366692
2017 Acid pretreatment and enzymatic saccharification of brown seaweed for polyhydroxybutyrate (PHB) production using Cupriavidus necator. International journal of biological macromolecules 36 28385521
2017 Controlling microbial PHB synthesis via CRISPRi. Applied microbiology and biotechnology 36 28620688
2009 Statistical media optimization for growth and PHB production from methanol by a methylotrophic bacterium. Bioresource technology 36 19121581
2004 Thermotolerant poly(3-hydroxybutyrate)-degrading bacteria from hot compost and characterization of the PHB depolymerase of Schlegelella sp. KB1a. Archives of microbiology 35 15340791
2014 Histological and molecular-biological analyses of poly(3-hydroxybutyrate) (PHB) patches for enhancement of bone regeneration. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 33 24862689
2009 Purification, immobilization, and characterization of nattokinase on PHB nanoparticles. Bioresource technology 33 19608412
2009 Production and characterization of PHB from two novel strains of Bacillus spp. isolated from soil and activated sludge. Journal of industrial microbiology & biotechnology 32 19953293
2023 PHB production from food waste hydrolysates by Halomonas bluephagenesis Harboring PHB operon linked with an essential gene. Metabolic engineering 28 36889504
2022 Finding of novel lactate utilizing Bacillus sp. YHY22 and its evaluation for polyhydroxybutyrate (PHB) production. International journal of biological macromolecules 28 35038470
2017 Effects of dietary poly-β-hydroxybutyrate (PHB) on microbiota composition and the mTOR signaling pathway in the intestines of litopenaeus vannamei. Journal of microbiology (Seoul, Korea) 28 29214487
2016 Understanding the physiological roles of polyhydroxybutyrate (PHB) in Rhodospirillum rubrum S1 under aerobic chemoheterotrophic conditions. Applied microbiology and biotechnology 28 27480532
2007 Engineering of PHB synthesis causes improved elastic properties of flax fibers. Biotechnology progress 28 17269698
2019 Enhanced production of poly‑3‑hydroxybutyrate (PHB) by expression of response regulator DR1558 in recombinant Escherichia coli. International journal of biological macromolecules 27 30851327
2022 CHCHD10 and SLP2 control the stability of the PHB complex: a key factor for motor neuron viability. Brain : a journal of neurology 25 35656794
2020 The Growth of 3T3 Fibroblasts on PHB, PLA and PHB/PLA Blend Films at Different Stages of Their Biodegradation In Vitro. Polymers 25 33383857
2013 Novel extracellular PHB depolymerase from Streptomyces ascomycinicus: PHB copolymers degradation in acidic conditions. PloS one 24 23951224
2004 The activator of the Rhodospirillum rubrum PHB depolymerase is a polypeptide that is extremely resistant to high temperature (121 degrees C) and other physical or chemical stresses. FEMS microbiology letters 24 14757249
2023 Plasma surface modification of electrospun polyhydroxybutyrate (PHB) nanofibers to investigate their performance in bone tissue engineering. International journal of biological macromolecules 23 36621738
2019 Enhancement of polyhydroxybutyrate (PHB) production by 10-fold from alkaline pretreatment liquor with an oxidative enzyme-mediator-surfactant system under Plackett-Burman and central composite designs. Bioresource technology 23 30807996
2018 Halomonas smyrnensis as a cell factory for co-production of PHB and levan. International journal of biological macromolecules 23 30001608
2015 Biosynthesis of poly-3-hydroxybutyrate (PHB) from glycerol by Paracoccus denitrificans in a batch bioreactor: effect of process variables. Preparative biochemistry & biotechnology 23 24547951
2014 Modeling pure culture heterotrophic production of polyhydroxybutyrate (PHB). Bioresource technology 23 24457311
2008 Effect of anaerobic promoters on the microaerobic production of polyhydroxybutyrate (PHB) in recombinant Escherichia coli. Applied microbiology and biotechnology 23 19107470
2023 PHB promotes bladder cancer cell epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway. Pathology, research and practice 22 37235908
2016 Effect of Polyhydroxybutyrate (PHB) storage on L-arginine production in recombinant Corynebacterium crenatum using coenzyme regulation. Microbial cell factories 22 26785743
2023 Poly(3-hydroxybutyrate) (PHB) and Polycaprolactone (PCL) Based Blends for Tissue Engineering and Bone Medical Applications Processed by FDM 3D Printing. Polymers 21 37242979
2018 Bradyrhizobium diazoefficiens USDA110 PhaR functions for pleiotropic regulation of cellular processes besides PHB accumulation. BMC microbiology 21 30355296
2023 The landscape of mitophagy in sepsis reveals PHB1 as an NLRP3 inflammasome inhibitor. Frontiers in immunology 20 37359543
2023 Polyhydroxybutyrate (PHB) production from sugar cane molasses and tap water without sterilization using novel strain, Priestia sp. YH4. International journal of biological macromolecules 20 37558031
2019 Purification and kinetics of the PHB depolymerase of Microbacterium paraoxydans RZS6 isolated from a dumping yard. PloS one 20 31211775
2017 Bacterial Community and PHB-Accumulating Bacteria Associated with the Wall and Specialized Niches of the Hindgut of the Forest Cockchafer (Melolontha hippocastani). Frontiers in microbiology 20 28293223
2007 Chemically inducible expression of the PHB biosynthetic pathway in Arabidopsis. Transgenic research 20 17279436
2024 Lycopene Protects against Atrazine-Induced Kidney STING-Dependent PANoptosis through Stabilizing mtDNA via Interaction with Sam50/PHB1. Journal of agricultural and food chemistry 19 38820047
2023 Inhibition of MYC translation through targeting of the newly identified PHB-eIF4F complex as a therapeutic strategy in CLL. Blood 19 37084385
2022 Effect of recombinant BMP-2 and erythropoietin on osteogenic properties of biomimetic PLA/PCL/HA and PHB/HA scaffolds in critical-size cranial defects model. Materials science & engineering. C, Materials for biological applications 19 35581092
2015 The evaluation of physical properties and in vitro cell behavior of PHB/PCL/sol-gel derived silica hybrid scaffolds and PHB/PCL/fumed silica composite scaffolds. Colloids and surfaces. B, Biointerfaces 18 26364089
2012 Proteomic analysis of Bacillus thuringiensis ΔphaC mutant BMB171/PHB(-1) reveals that the PHB synthetic pathway warrants normal carbon metabolism. Journal of proteomics 18 22705120
2004 Roles of poly(3-hydroxybutyrate) depolymerase and 3HB-oligomer hydrolase in bacterial PHB metabolism. Current microbiology 18 15170237
2023 Polyhydroxybutyrate (PHB) in nanoparticulate form improves physical and biological performance of scaffolds. International journal of biological macromolecules 17 36870657
2022 Isolation and optimization of extracellular PHB depolymerase producer Aeromonas caviae Kuk1-(34) for sustainable solid waste management of biodegradable polymers. PloS one 17 35421107
2021 STOML2 interacts with PHB through activating MAPK signaling pathway to promote colorectal Cancer proliferation. Journal of experimental & clinical cancer research : CR 17 34781982
2020 HDAC6 promotes sepsis development by impairing PHB1-mediated mitochondrial respiratory chain function. Aging 17 32221047
2017 Cloning of phaCAB genes from thermophilic Caldimonas manganoxidans in Escherichia coli for poly(3-hydroxybutyrate) (PHB) production. Applied microbiology and biotechnology 17 28664325
2022 Phytoestrogen arctigenin preserves the mucus barrier in inflammatory bowel diseases by inhibiting goblet cell apoptosis via the ERβ/TRIM21/PHB1 pathway. Phytotherapy research : PTR 16 35599350
2022 Novel approach based on GQD-PHB as anchoring platform for the development of SARS-CoV-2 electrochemical immunosensor. Analytica chimica acta 16 36257733
2020 Biocompatible PHB Production from Bacillus Species Under Submerged and Solid-State Fermentation and Extraction Through Different Downstream Processing. Current microbiology 16 32095890
2020 Preparation and characterisation of organic UV filters based on combined PHB/liposomes with natural phenolic compounds. Journal of biotechnology 16 34154737
2014 Biosynthesis of poly(3-hydroxybutyrate) (PHB) by Cupriavidus necator H16 from jatropha oil as carbon source. Bioprocess and biosystems engineering 16 24078185
2014 Poly-β-hydroxybutyrate (PHB) accumulating Bacillus spp. improve the survival, growth and robustness of Penaeus monodon (Fabricius, 1798) postlarvae. Veterinary microbiology 16 25213234
2014 Impact of Ralstonia eutropha's poly(3-Hydroxybutyrate) (PHB) Depolymerases and Phasins on PHB storage in recombinant Escherichia coli. Applied and environmental microbiology 16 25281380
2016 Prohibitin( PHB) roles in granulosa cell physiology. Cell and tissue research 15 26496733
2023 Osteogenic potential of PHB-lignin/cellulose nanofiber electrospun scaffold as a novel bone regeneration construct. International journal of biological macromolecules 14 37532195
2022 Polyhydroxybutyrate (PHB)-Based Biodegradable Polymer from Agromyces indicus: Enhanced Production, Characterization, and Optimization. Polymers 14 36235929
2021 The Ethyl Acetate Extract From Celastrus orbiculatus Promotes Apoptosis of Gastric Cancer Cells Through Mitochondria Regulation by PHB. Frontiers in pharmacology 14 34122065
2024 Prohibitins, Phb1 and Phb2, function as Atg8 receptors to support yeast mitophagy and also play a negative regulatory role in Atg32 processing. Autophagy 13 38964378
2023 Evaluation of Biocompatibility of PLA/PHB/TPS Polymer Scaffolds with Different Additives of ATBC and OLA Plasticizers. Journal of functional biomaterials 13 37623657
2016 Backup Expression of the PhaP2 Phasin Compensates for phaP1 Deletion in Herbaspirillum seropedicae, Maintaining Fitness and PHB Accumulation. Frontiers in microbiology 13 27242754
2015 Poly(-β-hydroxybutyrate) (PHB) depolymerase PHAZ Pen from Penicillium expansum: purification, characterization and kinetic studies. 3 Biotech 13 28324398
2021 Polyhydroxybutyrate (PHB) Production Using an Arabinose-Inducible Expression System in Comparison With Cold Shock Inducible Expression System in Escherichia coli. Frontiers in bioengineering and biotechnology 12 34012957
2017 PHB in Cardiovascular and Other Diseases: Present Knowledge and Implications. Current drug targets 12 27557820