Affinage

RAD23B

Lysine-specific demethylase RAD23B · UniProt P54727

Length
409 aa
Mass
43.2 kDa
Annotated
2026-06-10
68 papers in source corpus 40 papers cited in narrative 40 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

RAD23B is a multidomain adaptor that bridges global-genome nucleotide excision repair (NER) and the ubiquitin-proteasome system (PMID:8756644, PMID:23897431). In NER, it forms a tight complex with XPC, stimulating XPC-dependent damage recognition through a 56-residue amphipathic XPC-binding domain that is necessary and sufficient for both binding and repair stimulation (PMID:9372923, PMID:15885096). The XPC-RAD23B complex binds diverse bulky and helix-distorting lesions with nanomolar affinity and high specificity over undamaged DNA, with damage discrimination driven primarily by DNA structural distortion rather than adduct chemistry (PMID:12022861, PMID:16460043, PMID:17525733); within the complex XPC makes the direct DNA contacts while RAD23B interacts with DNA largely indirectly (PMID:17320292). Recognition proceeds through hopping-based one-dimensional diffusion that allows lesion search and interrogation (PMID:31372632), with dissociation kinetics being rate-limiting for repair of certain lesions (PMID:27327897), and the complex recruits TFIIH to damaged DNA via XPC contacts with XPB/p62 to nucleate downstream repair assembly (PMID:10734143). In its second role, RAD23B acts as a proteasome shuttle factor: its N-terminal ubiquitin-like (UbL) domain mimics ubiquitin to bind the proteasome subunit S5a, while its UBA domains engage K48-linked polyubiquitin and inhibit chain extension, with an intramolecular UbL-UBA interaction modulating these contacts (PMID:12832454, PMID:14585839). Consistent with this, the majority of RAD23B interactors are ubiquitin-proteasome components, and loss of Rad23b in mice impairs erythropoiesis through a proteasome-dependent mechanism while NER remains intact owing to redundancy with Rad23a (PMID:23897431). RAD23B levels and activity are tuned by post-translational and spatial control: PARP1 PARylates the complex to reduce DNA binding (PMID:26170451), PSMD7 stabilizes RAD23B by preventing its degradation (PMID:34512150), OTUD1 directs RAD23B-XPC for proteasomal degradation through ubiquitin-chain editing (PMID:41286308), and the localization regulators PAQR3 and HDAC6 sequester RAD23B at the Golgi or cytoplasm to limit XPC stabilization and proteasome cargo shuttling (PMID:28473198, PMID:23703321, PMID:38747592). RAD23B also engages polyglutamine disease proteins, binding ataxin-3 via its UbL domain and being sequestered into polyQ inclusions through its UBA domains, linking it to substrate handling in neurodegeneration (PMID:10915768, PMID:29401586). Beyond these core roles, individual studies implicate RAD23B in p53 stabilization after genotoxic stress, cancer-cell invasion via CORO1C, and a vertebrate-derived copper-binding metalloadaptor function (PMID:16924240, PMID:34062216, PMID:40972527).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    Established that RAD23B is a functional cofactor of XPC rather than an isolated repair factor, defining its primary role in stimulating global-genome NER.

    Evidence Reconstituted in vitro NER assay with recombinant proteins in fractionated XP-C extracts across multiple lesion types

    PMID:8756644

    Open questions at the time
    • Did not map the interaction interface
    • In vitro stimulation did not address in vivo requirement given Rad23a redundancy
  2. 1997 High

    Mapped the molecular basis of the XPC interaction, showing a discrete amphipathic helical domain is necessary and sufficient for XPC binding and NER stimulation.

    Evidence Deletion mutagenesis, His-tagged pulldowns, in vitro NER stimulation, and yeast two-hybrid domain mapping

    PMID:9164480 PMID:9372923

    Open questions at the time
    • Two-hybrid functional correlation was indirect
    • Did not resolve how the domain stabilizes XPC
  3. 2000 High

    Connected the XPC-RAD23B complex to downstream repair assembly by showing it recruits TFIIH to damaged DNA, and identified UbL binding to disease protein ataxin-3.

    Evidence Reciprocal Co-IP and cell-free reconstitution showing TFIIH recruitment defect; yeast two-hybrid plus immunofluorescence for ataxin-3

    PMID:10734143 PMID:10915768

    Open questions at the time
    • TFIIH contact attributed to XPC, not RAD23B directly
    • Ataxin-3 interaction functional consequence not established at this stage
  4. 2002 High

    Quantified the affinity and specificity of damage recognition, demonstrating lesion preference and strong discrimination against undamaged DNA.

    Evidence Fluorescence anisotropy equilibrium binding and competition with defined damaged substrates

    PMID:12022861

    Open questions at the time
    • Did not resolve whether specificity arises from chemistry or DNA distortion
    • Kinetic basis of discrimination not addressed
  5. 2003 High

    Defined the structural and proteasome-targeting roles of the UbL/UBA domains, showing UbL mimics ubiquitin to bind S5a while UBA inhibits chain assembly.

    Evidence NMR structures of UbL and UIM:UbL complexes with chemical-shift and mutagenesis mapping; SFM of DNA bending

    PMID:12547395 PMID:12832454 PMID:14585839

    Open questions at the time
    • Did not connect proteasome shuttling to specific in vivo substrates
    • DNA bending role inferred, not functionally tested
  6. 2006 Medium

    Resolved damage discrimination kinetics and began distinguishing paralog-specific proteasome behavior and a role in damage-induced p53 stabilization.

    Evidence Stopped-flow pre-steady-state kinetics; paralog mutagenesis and co-purification; siRNA, ChIP and ubiquitin-mutant analysis of p53

    PMID:16460043 PMID:16712842 PMID:16924240

    Open questions at the time
    • p53 role from single lab without reciprocal validation
    • Mechanism linking RAD23B to p53 ubiquitin accumulation unresolved
  7. 2007 High

    Established that lesion stereochemistry and helix-opening govern XPC-RAD23B binding and NER efficiency, and showed XPC is the direct DNA-contacting subunit.

    Evidence Permanganate footprinting with reconstituted NER; site-specific photocrosslinking with denaturing IP

    PMID:17320292 PMID:17525733

    Open questions at the time
    • RAD23B's contribution to DNA contact remained indirect/unclear
    • Orientation specificity mechanism not structurally resolved
  8. 2013 High

    Demonstrated an in vivo proteasome-shuttling role distinct from NER, with the Rad23b interactome dominated by UPS components and erythropoiesis defects upon loss.

    Evidence Rad23b-null mouse with unbiased interactor proteomics, erythroid differentiation flow cytometry, and proteasome inhibition; HDAC6 Co-IP and interactome

    PMID:23703321 PMID:23897431

    Open questions at the time
    • Specific ubiquitinated cargoes in erythropoiesis not identified
    • HDAC6 regulation deacetylase-independent mechanism only partly defined
  9. 2015 Medium

    Identified PARylation as a post-translational regulator of DNA binding, with PAR competing with DNA for the complex.

    Evidence 32P-NAD+ incorporation, immunoblotting, and competitive binding assays

    PMID:26170451

    Open questions at the time
    • In vivo relevance of PARylation not established
    • Single-lab biochemistry without structural mapping of modified sites
  10. 2017 Medium

    Showed that subcellular compartmentation controls function: Golgi tethering by PAQR3 sequesters RAD23B and destabilizes XPC, reducing NER capacity.

    Evidence Co-IP, subcellular fractionation, ubiquitination and γ-H2AX assays with knockdown/overexpression

    PMID:28473198

    Open questions at the time
    • Single lab
    • Physiological trigger for PAQR3-mediated sequestration unknown
  11. 2019 High

    Defined the search mechanism of XPC-RAD23B at single-molecule resolution, showing hopping-based 1D diffusion and biphasic lesion interrogation.

    Evidence High-throughput DNA curtain single-molecule imaging with diffusion analysis

    PMID:31372632

    Open questions at the time
    • RAD23B-specific contribution to diffusion not isolated
    • Did not address handoff to downstream factors
  12. 2020 Medium

    Refined lesion-recognition rules by demonstrating competition with base-excision repair and a lesion-avoidance effect for stably stacked adducts.

    Evidence Competition binding with NEIL1 and single-turnover kinetics; fluorescence KD measurement with structural modeling; SPR koff analysis

    PMID:27327897 PMID:32302101 PMID:33035795

    Open questions at the time
    • In vivo pathway competition with BER not tested
    • Structural models not experimentally validated
  13. 2021 Medium

    Established RAD23B as a regulated node in cancer through stabilization by PSMD7 and as an adaptor in invasion signaling via CORO1C.

    Evidence Co-IP, ubiquitination assays, knockdown, and xenografts in gastric and colorectal cancer models

    PMID:34062216 PMID:34512150

    Open questions at the time
    • Direct deubiquitination of RAD23B by PSMD7 not biochemically reconstituted
    • CORO1C axis mechanism is correlative
  14. 2024 Medium

    Extended the HDAC6 axis and adaptor function, showing HDAC6-inhibitor-released RAD23B shuttles cargo affecting antigen presentation, and RAD23B serves as the ubiquitin adaptor for Twist1.

    Evidence Pharmacologic HDAC6 domain inhibition with proteasome, antigen-presentation and T-cell assays; Co-IP and ubiquitination assays for Twist1

    PMID:38747592 PMID:39582466

    Open questions at the time
    • Direct cargo identity in immune context incompletely defined
    • Twist1 adaptor role from single lab
  15. 2025 Medium

    Diversified the functional landscape with new partners (UV-DDB handoff, MINDY3, OTUD1), a copper-binding metalloadaptor function, and roles in aggregate clearance and phase separation.

    Evidence Single-molecule and biochemical UX-complex assays; crystal structure of MINDY3 UbL complex (preprint); ubiquitin-linkage analysis for OTUD1; structural/biochemical copper-binding and evolutionary analysis; live-cell imaging and LLPS assays

    PMID:40530698 PMID:40684934 PMID:40972527 PMID:41286308 PMID:42172862 PMID:bio_10.1101_2025.07.16.665128 PMID:bio_10.1101_2025.09.15.676044

    Open questions at the time
    • Copper metalloadaptor function is a single novel study requiring replication
    • Phase-separation and condensate roles are preprint/low-confidence
    • Integration of new partners into a unified regulatory model incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RAD23B's two functions — NER damage recognition and proteasomal substrate shuttling — are coordinated within a cell, and which determinants partition it between these roles, remains unresolved.
  • No unified model linking spatial regulation, PTMs, and substrate choice
  • RAD23B-specific in vivo proteasome substrates largely unidentified
  • Physiological relevance of copper-binding and phase-separation functions in humans untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-73894 DNA Repair 6 R-HSA-392499 Metabolism of proteins 5
Partners
ATXN3HDAC6OTUD1PAQR3PSMD4PSMD7TFIIHXPC
Complex memberships
UV-DDB/XPC-RAD23B (UX) complexXPC-RAD23B complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 HHR23B (RAD23B) stimulates XPC protein activity in nucleotide excision repair (NER) in vitro. In a reconstituted repair system lacking endogenous XPC and HHR23B, recombinant XPC alone weakly corrected NER defects, while co-addition of recombinant HHR23B significantly enhanced repair activity for both UV- and N-acetoxy-2-acetylfluorene-induced lesions on naked plasmid and SV40 minichromosomes. Reconstituted in vitro NER assay with recombinant proteins in fractionated XP-C cell extracts Molecular and cellular biology High 8756644
1997 A 56-amino-acid XPC-binding domain in hHR23B (residues covering this region) is both necessary and sufficient for binding XPC and stimulating NER in vitro. The domain has predominantly amphipathic alpha-helical character and binds XPC via hydrophobic interactions. Deletion mutagenesis, nickel-chelating Sepharose pulldown with His-tagged fragments, in vitro NER stimulation assay Molecular and cellular biology High 9372923
1997 XPC interacts in vivo with both HHR23B and HHR23A via the same conserved region in the C-terminal half of XPC, and an N-terminal region of HHR23B contains the XPC-interaction site. XPC mutants deficient in binding both RAD23 homologs are also highly defective in complementing XPC cells in vivo. Yeast two-hybrid system, domain mapping Mutation research Medium 9164480
2000 The XPC-HR23B complex interacts with general transcription factor IIH (TFIIH) both in vivo and in vitro, mediated through XPC affinity for TFIIH subunits XPB and/or p62. XPC-HR23B is required for efficient association of TFIIH with damaged DNA in cell-free extracts, establishing its role in recruiting TFIIH to sites of damage in global genome NER. Co-immunoprecipitation (in vivo and in vitro), cell-free repair reconstitution with XP-C and XP-A extracts The Journal of biological chemistry High 10734143
2000 Ataxin-3 interacts with the ubiquitin-like (UbL) domain at the N-terminus of HHR23B (and HHR23A). In 293 cells, mutant polyQ-expanded ataxin-3 recruits HHR23A to intranuclear inclusions via this interaction. Yeast two-hybrid screen, domain interaction mapping, immunofluorescence in transfected cells Human molecular genetics Medium 10915768
2002 The XPC-HR23B complex binds damaged DNA with high affinity (KD ~1–3 nM) and high specificity, showing ~30-fold preference for 6,4-photoproducts over cyclobutane dimers. The complex binds with high specificity over undamaged DNA (specificity factor 100–3000). Fluorescence anisotropy equilibrium binding assay, stoichiometric titration, competition with undamaged/damaged plasmid Biochemistry High 12022861
2003 XPC-HR23B induces a bend in DNA upon binding, and this bend is stabilized at the site of damage. DNA bending is proposed as an architectural feature exploited for assembly of subsequent NER complexes. Scanning force microscopy (SFM) of protein-DNA complexes DNA repair Medium 12547395
2003 The NMR structure of the UbL domain of hHR23B was determined. The UBA domains of hHR23B bind to ubiquitin at Lys-48, inhibiting multiubiquitin assembly, and an intramolecular UbL-UBA interaction was identified. The UbL domain binds the polyubiquitin-binding site 2 (PUbS2) of proteasome subunit S5a, mimicking ubiquitin. NMR structure determination, chemical shift perturbation binding mapping The Journal of biological chemistry High 12832454
2003 Crystal/NMR structure of the ubiquitin-interacting motif (UIM) of proteasome subunit S5a bound to the UbL domain of HR23B was determined, revealing one hydrophobic and two polar contact sites. The UbL domain mimics ubiquitin in binding UIM; a histidine residue in ubiquitin confers pH-dependent binding differences. NMR structure of UIM:UbL complex, mutagenesis The Journal of biological chemistry High 14585839
2005 Solution NMR structure of the XPC-binding domain (XPCB, residues 275–342) of hHR23B was determined. The domain forms kinked alpha-helices with periodic prolines; the N-terminal region (residues 275–283) is more flexible than the corresponding region of hHR23A, potentially contributing to functional differences between the two paralogs. NMR structure determination, 15N relaxation backbone dynamics The FEBS journal High 15885096
2005 XPC-hHR23B recognizes psoralen interstrand crosslinks with high affinity and specificity. XPC-hHR23B and XPA-RPA can bind psoralen ICLs simultaneously, forming a multimeric complex on damaged DNA. Electrophoretic mobility shift assay, simultaneous binding assay with multiple purified NER proteins Nucleic acids research Medium 15914671
2005 hHR23B localizes to both nucleus and cytoplasm during G1 phase; nuclear levels decrease during S-phase; during mitosis, hHR23B relocalizes entirely to the cytoplasm without association with chromatin. This distribution is cell cycle dependent. Immunofluorescence across cell cycle phases Biochemical and biophysical research communications Medium 16253613
2006 XPC-hHR23B displays faster association rate (kon) for cisplatin- and UV-damaged duplex DNA than for undamaged DNA. XPC-hHR23B has high affinity for undamaged single-stranded DNA mainly through a high kon; cisplatin damage on ssDNA reduces binding ~7-fold via effects on both kon and koff. Damage discrimination is driven primarily by structural changes in DNA, not adduct chemistry. Stopped-flow fluorescence pre-steady-state kinetics Biochemistry High 16460043
2006 hHR23A and hHR23B form distinct interactions with proteasomes and multiubiquitinated proteins. Threonine-79 in hHR23A weakens its proteasome binding relative to hHR23B (which has proline at that position); T79P mutation in hHR23A increases proteasome interaction. Both paralogs bind Ataxin-3 similarly but co-purify with unique proteolytic factors in vivo. Mutagenesis, co-purification from human breast cancer tissue, binding assays FEBS letters Medium 16712842
2006 hHR23B is required for genotoxin-induced stabilization and activation of p53. siRNA depletion of hHR23B abrogated accumulation of ubiquitinated p53, attenuated p53/p21/bax induction, and suppressed apoptosis after DNA damage. K48-linked p53-ubiquitin conjugates were specifically induced after genotoxic stress, and hHR23B accumulated with ubiquitinated p53 in chromatin and at the p21 promoter. siRNA knockdown, chromatin immunoprecipitation, ubiquitin lysine-mutant expression constructs, flow cytometry for apoptosis Oncogene Medium 16924240
2007 XPC/HR23B exhibits distinct helix-opening patterns on three stereoisomeric benzo[a]pyrene-N2-dG lesions, as revealed by permanganate footprinting. The extent of helix opening and overall XPC/HR23B binding correlates with dual incision efficiency by reconstituted NER, demonstrating that lesion stereochemistry determines XPC binding and NER efficiency. Permanganate footprinting, in vitro NER reconstitution with purified factors, cell-free extract NER The EMBO journal High 17525733
2007 Photocrosslinking assays with damaged DNA substrates demonstrated that XPC is the subunit of XPC-HR23B that directly contacts DNA (both damaged and complementary strands), while Rad23B interaction with DNA is largely indirect via XPC. XPC-Rad23B complex preferentially crosslinks 5' of the cisplatin adduct, suggesting orientation-specific binding. Photocrosslinking with photoreactive dNMP analogues, denaturing immunoprecipitation of protein-DNA complexes Biochimica et biophysica acta Medium 17320292
2010 HR23B governs the sensitivity of CTCL cells to HDAC inhibitors. HR23B depletion reduces HDAC inhibitor-induced apoptosis, and HDAC inhibitor treatment deregulates proteasome activity through a mechanism dependent on HR23B. Genome-wide loss-of-function screen, siRNA knockdown, cell death assays in CTCL lines Proceedings of the National Academy of Sciences of the United States of America Medium 20308564
2010 XPC-Rad23B makes direct contact with both the cisplatin-damaged DNA strand and the complementary undamaged strand. Rad23B's interaction with DNA is largely indirect, mediated through XPC. The complex shows orientation-specific binding, preferentially crosslinking 5' of the cisplatin adduct. Photo-crosslinking with FAP-dCMP analogue at defined positions, immunoprecipitation after denaturation Biochemistry Medium 20028083
2013 HDAC6 interacts with HR23B and downregulates HR23B protein levels independently of its deacetylase activity, reducing ubiquitinated substrates targeted to the proteasome and desensitizing cells to apoptosis. HSP90 was identified as a key effector mediating HDAC6's effect on HR23B levels. Co-immunoprecipitation, HDAC6 interactome analysis (MS), overexpression/knockdown with apoptosis/autophagy readouts, deacetylase-inactive mutant Cell death and differentiation Medium 23703321
2013 Rad23b-null mice are proficient in NER (due to redundancy with Rad23a) but show defective erythropoiesis. The majority of Rad23b-interacting proteins identified by unbiased proteomics are associated with the ubiquitin-proteasome system (UPS). Loss of Rad23b reduces cell proliferation in fibroblasts, causes accumulation of early erythroid progenitors, and blocks erythroid maturation in fetal liver. Proteasome inhibition recapitulates Rad23b loss in erythroid cells. Knockout mouse model, unbiased proteomics of Rad23b interactors, cell proliferation assays, flow cytometry of erythroid differentiation, siRNA knockdown Molecular and cellular biology High 23897431
2015 Both XPC and RAD23B subunits of the XPC-RAD23B complex are poly(ADP-ribosyl)ated by PARP1 in vitro. Free PAR competes with DNA for XPC-RAD23B binding in an affinity-dependent manner. The efficiency of PARylation of XPC-RAD23B increases after UV irradiation of DNA substrate. 32P-labeled NAD+ incorporation assay, immunoblotting, competitive binding assays The Journal of biological chemistry Medium 26170451
2015 YB-1 and XPC-HR23B mutually stimulate each other's binding to DNA containing bulky lesions or clustered lesions (bulky lesion plus abasic site), suggesting YB-1 functions as a modulator of NER damage recognition. Photocrosslinking and binding assays with purified proteins and defined damaged DNA substrates Biochemistry (Biokhimiia) Low 25756536
2016 The dissociation rate (koff) of XPC-RAD23B from damaged DNA inversely correlates with NER efficiency; XPC retention on clustered adducts is much longer than on mono-adducts, making dissociation a rate-limiting step for NER of certain lesions. Surface plasmon resonance (real-time kinetics), comparison of mono- vs di-AAF-modified substrates PloS one Medium 27327897
2017 PAQR3 directly associates with RAD23B and tethers it to the Golgi apparatus, reducing nuclear RAD23B levels. This reduces the amount of RAD23B available to stabilize XPC, leading to enhanced polyubiquitination and degradation of XPC and diminished NER capacity. Subcellular compartmentation of RAD23B thus controls XPC stability. Co-immunoprecipitation, subcellular fractionation, ubiquitination assay, siRNA knockdown/overexpression, γ-H2AX immunoblotting for DNA damage Cellular signalling Medium 28473198
2018 PolyQ-expanded huntingtin and ataxin-3 sequester hHR23B into inclusions through the UBA domains of hHR23B binding conjugated ubiquitin on the aggregated proteins. This sequestration reduces available hHR23B and consequently decreases XPC protein levels. Cell transfection, immunofluorescence, Western blotting, domain mutant analysis FASEB journal Medium 29401586
2019 Single-molecule imaging revealed that XPC-RAD23B diffuses along DNA via hopping (one-dimensional motion), allowing it to bypass protein obstacles during damage search. XPC-RAD23B makes futile attempts to bind CPDs (consistent with low CPD recognition efficiency) and binds CPDs in biphasic states — stable for lesion recognition and transient for lesion interrogation. High-throughput single-molecule imaging (DNA curtain assay), diffusion coefficient analysis under varying ionic strengths Nucleic acids research High 31372632
2020 XPC-RAD23B (XPC) competes with the BER glycosylase NEIL1 for binding to hydantoin DNA lesions (spiroiminodihydantoin and 5-guanidinohydantoin). XPC displaces non-covalently bound NEIL1 from these lesions at [XPC]/[NEIL1] ratios >0.2, inhibiting NEIL1 BER activity, with lesion incision only resuming after XPC dissociation. Competition binding assay with purified proteins, single-turnover NEIL1 incision kinetics in the presence of varying XPC concentrations Biochemistry Medium 32302101
2020 Deleting a single cytosine opposite a bulky B[a]P-dG lesion in a 50-mer duplex fully abrogates XPC-RAD23B binding. XPC shows slightly lower affinity (2.5–3.6-fold higher KD) for G*:deletion duplexes than for undamaged G:deletion duplexes — a lesion-avoidance effect attributed to thermodynamic stabilization by base stacking of the B[a]P aromatic ring system preventing DNA distortion required for XPC's BHD2/BHD3 hairpin binding. Fluorescence binding assay with competitor DNA to determine accurate KD values, structural modeling DNA repair Medium 33035795
2021 PSMD7, a deubiquitinase, directly interacts with RAD23B and prevents its ubiquitination and proteasomal degradation, thereby stabilizing RAD23B and the RAD23B-XPC complex. PSMD7 knockdown enhances ubiquitination and degradation of RAD23B in gastric cancer cells and reduces cisplatin resistance. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, xenograft mouse model International journal of biological sciences Medium 34512150
2021 RAD23B interacts and co-localizes with CORO1C in the cytoplasm of colorectal cancer cells. Overexpression of RAD23B and/or CORO1C increases invadopodia formation and matrix degradation, while RAD23B knockdown suppresses the talin1/2-integrin/FAK/RhoA/Rac1/CORO1C signaling axis and inhibits invasion and metastasis. Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, invasion/migration assays in vitro and xenograft Cancer letters Medium 34062216
2024 HDAC6 inhibition releases HR23B from HDAC6 sequestration via the HDAC6 ubiquitin-binding domain, allowing HR23B to shuttle ubiquitinylated cargo to proteasomes. Silencing HDAC6 or HR23B in myeloma cells abolishes the effect of HDAC6 inhibitors on proteasome activity, antigen presentation, and T-cell cytotoxicity. Pharmacologic HDAC6 domain inhibition, siRNA knockdown, proteasome activity assay, MHC-I antigen presentation assay, T-cell cytotoxicity assay Cancer research communications Medium 38747592
2024 FMNL3 directly interacts with Twist1 and suppresses Twist1 ubiquitin-dependent degradation by inhibiting the interaction between Twist1 and RAD23B, the ubiquitin transfer protein for Twist1, thereby promoting EMT and breast cancer cell invasion. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown/overexpression, invasion assay Journal of cellular physiology Medium 39582466
2025 XPC-RAD23B enhances UV-DDB binding to DNA by forming a UV-DDB/XPC-RAD23B (UX) complex. The UX-complex increases UV-DDB affinity for undamaged DNA and facilitates UV-DDB one-dimensional diffusion along DNA for CPD search. UV-DDB and XPC-RAD23B can bind CPDs as a complex, facilitating lesion transfer. Biochemical binding assays, single-molecule DNA curtain assay, 1D diffusion analysis Nucleic acids research High 40530698
2025 RAD23B acquires an allosteric H274/H323 copper-binding site in the transition from amphibians to reptiles, enabling it to transfer copper from CTR1 to all known copper metallochaperone pathways while making its canonical DNA repair functions copper-dependent. Structural and biochemical characterization of copper binding, evolutionary comparative analysis, metabolic and DNA repair functional assays Molecular cell Medium 40972527
2025 OTUD1 deubiquitinase promotes degradation of the RAD23B-XPC complex by cleaving K63-linked ubiquitin chains on RAD23B and XPC and enhancing PRKN-mediated K48-linked ubiquitination, leading to proteasomal degradation. Loss of OTUD1 (via promoter methylation) stabilizes RAD23B-XPC and confers cisplatin resistance in NSCLC. Co-immunoprecipitation, ubiquitin linkage-specific analysis, overexpression/knockdown, in vitro and in vivo cisplatin sensitivity assays Oncogene Medium 41286308
2025 Rad23b directly interacts with mutant ataxin-3 (mATXN3), promotes its ubiquitination, and facilitates delivery to the proteasome; however, Rad23b paradoxically disrupts proteasome catalytic activity, preventing mATXN3 degradation and exacerbating aggregate formation. Rad23b knockdown/knockout reduces mATXN3 aggregates and neuronal cell death. Overexpression and knockdown/knockout functional assays, ubiquitination assay, co-immunoprecipitation, proteasome activity assay, immunohistochemistry in SCA3 transgenic mice Neurotherapeutics Medium 42172862
2025 The EF-hand insertion domain of MINDY3 deubiquitinase specifically binds the UbL domain of RAD23B (and RAD23A), but not other UBL-domain proteins. This interaction mediates MINDY3 recruitment to DNA damage sites. MINDY3 can form a ternary complex with RAD23A/B and polyubiquitin, and may deubiquitylate RAD23A/B-bound clients. Crystal structure of MINDY3 EF-hand:RAD23A UbL complex, Co-IP in cells, biochemical binding assays, DNA damage localization assay bioRxivpreprint Medium bio_10.1101_2025.07.16.665128
2025 RAD23B is necessary for the formation of transient aggregate-associated proteasome condensates (TAADs) that co-localize with cytosolic alpha-synuclein aggregates to facilitate their clearance via the ubiquitin-proteasome system. Quantitative live-cell imaging, siRNA knockdown, proteasome activity assay, proteomics bioRxivpreprint Low bio_10.1101_2025.09.15.676044
2025 Rad23B inhibits Ataxin-3 droplet maturation (liquid-to-solid phase transition) through heterotypic interactions but does not inhibit amyloid formation under dilute conditions, suggesting aggregation via misfolding is distinct from condensation pathway. In vitro LLPS assay, Thioflavin-T binding, co-incubation of purified proteins Journal of molecular biology Low 40684934

Source papers

Stage 0 corpus · 68 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 The xeroderma pigmentosum group C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA. The Journal of biological chemistry 222 10734143
1996 HHR23B, a human Rad23 homolog, stimulates XPC protein in nucleotide excision repair in vitro. Molecular and cellular biology 143 8756644
2000 Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B. Human molecular genetics 127 10915768
2010 HR23B is a biomarker for tumor sensitivity to HDAC inhibitor-based therapy. Proceedings of the National Academy of Sciences of the United States of America 123 20308564
2003 Critical DNA damage recognition functions of XPC-hHR23B and XPA-RPA in nucleotide excision repair. Molecular carcinogenesis 102 12949838
2003 Binding surface mapping of intra- and interdomain interactions among hHR23B, ubiquitin, and polyubiquitin binding site 2 of S5a. The Journal of biological chemistry 97 12832454
1997 Identification and characterization of XPC-binding domain of hHR23B. Molecular and cellular biology 94 9372923
2009 Laryngeal cancer risk associated with smoking and alcohol consumption is modified by genetic polymorphisms in ERCC5, ERCC6 and RAD23B but not by polymorphisms in five other nucleotide excision repair genes. International journal of cancer 86 19444904
2002 The XPC-HR23B complex displays high affinity and specificity for damaged DNA in a true-equilibrium fluorescence assay. Biochemistry 83 12022861
2003 DNA bending by the human damage recognition complex XPC-HR23B. DNA repair 80 12547395
2007 The human DNA repair factor XPC-HR23B distinguishes stereoisomeric benzo[a]pyrenyl-DNA lesions. The EMBO journal 77 17525733
2003 Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B. The Journal of biological chemistry 71 14585839
2018 Molecular basis for damage recognition and verification by XPC-RAD23B and TFIIH in nucleotide excision repair. DNA repair 63 30174301
2019 Circular RNA circ-RAD23B promotes cell growth and invasion by miR-593-3p/CCND2 and miR-653-5p/TIAM1 pathways in non-small cell lung cancer. Biochemical and biophysical research communications 60 30722989
2005 Human XPC-hHR23B interacts with XPA-RPA in the recognition of triplex-directed psoralen DNA interstrand crosslinks. Nucleic acids research 57 15914671
2019 Single-molecule visualization reveals the damage search mechanism for the human NER protein XPC-RAD23B. Nucleic acids research 55 31372632
1997 XPC interacts with both HHR23B and HHR23A in vivo. Mutation research 46 9164480
2011 Vorinostat/SAHA-induced apoptosis in malignant mesothelioma is FLIP/caspase 8-dependent and HR23B-independent. European journal of cancer (Oxford, England : 1990) 40 22154545
2004 Epigenetic silencing of the human nucleotide excision repair gene, hHR23B, in interleukin-6-responsive multiple myeloma KAS-6/1 cells. The Journal of biological chemistry 39 15550378
2006 Pre-steady-state binding of damaged DNA by XPC-hHR23B reveals a kinetic mechanism for damage discrimination. Biochemistry 38 16460043
2013 A regulatory circuit that involves HR23B and HDAC6 governs the biological response to HDAC inhibitors. Cell death and differentiation 37 23703321
2009 Binding of the human nucleotide excision repair proteins XPA and XPC/HR23B to the 5R-thymine glycol lesion and structure of the cis-(5R,6S) thymine glycol epimer in the 5'-GTgG-3' sequence: destabilization of two base pairs at the lesion site. Nucleic acids research 32 19892827
2015 Poly(ADP-ribose) Polymerase 1 Modulates Interaction of the Nucleotide Excision Repair Factor XPC-RAD23B with DNA via Poly(ADP-ribosyl)ation. The Journal of biological chemistry 31 26170451
2006 Evidence for distinct functions for human DNA repair factors hHR23A and hHR23B. FEBS letters 30 16712842
2021 Deubiquitinase PSMD7 promotes the proliferation, invasion, and cisplatin resistance of gastric cancer cells by stabilizing RAD23B. International journal of biological sciences 29 34512150
2018 PolyQ-expanded huntingtin and ataxin-3 sequester ubiquitin adaptors hHR23B and UBQLN2 into aggregates via conjugated ubiquitin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 29401586
2016 Two mammalian homologs of yeast Rad23, HR23A and HR23B, as multifunctional proteins. Gene 27 27771451
2014 Identification and functional validation of RAD23B as a potential protein in human breast cancer progression. Journal of proteome research 27 24897598
2021 Cytoplasmic RAD23B interacts with CORO1C to synergistically promote colorectal cancer progression and metastasis. Cancer letters 25 34062216
2007 Crosslinking of the NER damage recognition proteins XPC-HR23B, XPA and RPA to photoreactive probes that mimic DNA damages. Biochimica et biophysica acta 25 17320292
2008 Interaction of nucleotide excision repair factors XPC-HR23B, XPA, and RPA with damaged DNA. Biochemistry. Biokhimiia 24 18774935
2004 NMR structure of the DNA decamer duplex containing double T*G mismatches of cis-syn cyclobutane pyrimidine dimer: implications for DNA damage recognition by the XPC-hHR23B complex. Nucleic acids research 24 15121904
2006 hHR23B is required for genotoxic-specific activation of p53 and apoptosis. Oncogene 22 16924240
2018 MicroRNA-196b enhances the radiosensitivity of SNU-638 gastric cancer cells by targeting RAD23B. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 29864624
2011 Differential contribution of XPC, RAD23A, RAD23B and CENTRIN 2 to the UV-response in human cells. DNA repair 21 21676658
2013 Genetic polymorphisms in RAD23B and XPC modulate DNA repair capacity and breast cancer risk in Puerto Rican women. Molecular carcinogenesis 19 23776089
2017 Subcellular distribution of RAD23B controls XPC degradation and DNA damage repair in response to chemotherapy drugs. Cellular signalling 17 28473198
2022 Knockdown of circ-RAD23B inhibits non-small cell lung cancer progression via the miR-142-3p/MAP4K3 axis. Thoracic cancer 16 35106926
2010 Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals contacts with both strands of the DNA duplex and spans the DNA adduct. Biochemistry 16 20028083
2001 Microsatellite-containing genes from the channel catfish brain: evidence of trinucleotide repeat expansion in the coding region of nucleotide excision repair gene RAD23B. Biochemical and biophysical research communications 16 11716474
2021 Irisin attenuates lipopolysaccharide-induced acute lung injury by downregulating inflammatory cytokine expression through miR-199a-mediated Rad23b overexpression. Experimental cell research 15 33961841
2019 HR23B pathology preferentially co-localizes with p62, pTDP-43 and poly-GA in C9ORF72-linked frontotemporal dementia and amyotrophic lateral sclerosis. Acta neuropathologica communications 15 30867060
2016 HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat. The journal of pathology. Clinical research 14 27499916
2005 Solution structure and backbone dynamics of the XPC-binding domain of the human DNA repair protein hHR23B. The FEBS journal 14 15885096
2022 Identifying a novel KLF2/lncRNA SNHG12/miR-494-3p/RAD23B axis in Spare Nerve Injury-induced neuropathic pain. Cell death discovery 13 35624111
2015 Y-box binding protein 1 (YB-1) promotes detection of DNA bulky lesions by XPC-HR23B factor. Biochemistry. Biokhimiia 13 25756536
2008 Fluorescence correlation spectroscopy of the binding of nucleotide excision repair protein XPC-hHr23B with DNA substrates. Journal of fluorescence 11 18574675
2019 Contribution of STAT3 and RAD23B in Primary Sézary Cells to Histone Deacetylase Inhibitor FK228 Resistance. The Journal of investigative dermatology 10 30910759
2016 Dissociation Dynamics of XPC-RAD23B from Damaged DNA Is a Determining Factor of NER Efficiency. PloS one 10 27327897
2013 Erythropoietic defect associated with reduced cell proliferation in mice lacking the 26S proteasome shuttling factor Rad23b. Molecular and cellular biology 10 23897431
2016 Interaction of Nucleotide Excision Repair Protein XPC-RAD23B with DNA Containing Benzo[a]pyrene-Derived Adduct and Apurinic/Apyrimidinic Site within a Cluster. Biochemistry. Biokhimiia 9 27262192
2005 Studies on the intracellular localization of hHR23B. Biochemical and biophysical research communications 9 16253613
2004 Expression of a novel RAD23B mRNA splice variant in the human testis. Journal of andrology 9 15064313
2024 HDAC6 Inhibition Releases HR23B to Activate Proteasomes, Expand the Tumor Immunopeptidome and Amplify T-cell Antimyeloma Activity. Cancer research communications 8 38747592
2020 Inhibition of Excision of Oxidatively Generated Hydantoin DNA Lesions by NEIL1 by the Competitive Binding of the Nucleotide Excision Repair Factor XPC-RAD23B. Biochemistry 7 32302101
2020 The DNA damage-sensing NER repair factor XPC-RAD23B does not recognize bulky DNA lesions with a missing nucleotide opposite the lesion. DNA repair 5 33035795
2019 Upregulation of GRIM-19 augments the sensitivity of prostate cancer cells to docetaxel by targeting Rad23b. Clinical and experimental pharmacology & physiology 5 31531888
2018 Serum starvation raises turnover of phosphorylated p62/SQSTM1 (Serine 349), reveals expression of proteasome and N-glycanase1 interactive protein RAD23B and sensitizes human synovial fibroblasts to BAY 11-7085-induced cell death. Oncotarget 5 30533198
2025 XPC-RAD23B enhances UV-DDB binding to DNA to facilitate lesion search in nucleotide excision repair. Nucleic acids research 4 40530698
2021 A Phase 2a cohort expansion study to assess the safety, tolerability, and preliminary efficacy of CXD101 in patients with advanced solid-organ cancer expressing HR23B or lymphoma. BMC cancer 4 34301221
2024 RAD23B mediated proteasomal degradation occurs through p38 MAPK/ATF-2/RAD23B axis under nutrient-deprived conditions in breast cancer. Cell biology international 3 38561940
2024 FMNL3 Promotes Migration and Invasion of Breast Cancer Cells via Inhibiting Rad23B-Induced Ubiquitination of Twist1. Journal of cellular physiology 3 39582466
2025 RAD23B acquires a copper metalloadaptor function in amphibian-to-reptile evolution to increase metabolism and regulate genomic integrity. Molecular cell 2 40972527
2025 Rad23B Delays Ataxin-3 Liquid-to-solid Phase Transition Through Heterotypic Buffering. Journal of molecular biology 1 40684934
2026 Rad23b exacerbates pathological aggregates through disrupting proteasome functions in Spinocerebellar ataxia type 3. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 0 42172862
2025 RAD23B Promotes Colorectal Cancer Metastasis via the Talin1/Integrin/PI3K/AKT/MMP9 Axis. Oncology research 0 41179295
2025 The deubiquitinase OTUD1 orchestrates cisplatin chemosensitivity of non-small cell lung cancer through destabilizing RAD23B/XPC. Oncogene 0 41286308
2025 Bta-miR-30f promotes adipogenesis and unsaturated fatty acid accumulation by targeting RAD23B in buffalo intramuscular preadipocytes. iScience 0 41585475

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