Ask about this productRelated genes to: RAD23A Blocking Peptide
- Gene:
- RAD23A NIH gene
- Name:
- RAD23 homolog A, nucleotide excision repair protein
- Previous symbol:
- -
- Synonyms:
- HHR23A, MGC111083
- Chromosome:
- 19p13.13
- Locus Type:
- gene with protein product
- Date approved:
- 1994-07-20
- Date modifiied:
- 2016-10-05
Related products to: RAD23A Blocking Peptide
Related articles to: RAD23A Blocking Peptide
- The MINDY family of deubiquitinases (DUBs) are exemplified by their preference for cleaving K48-linked polyubiquitin. MINDY3 is architecturally distinct from other MINDY DUBs as its catalytic domain spans the entire length of the protein except for an atypical EF-hand insertion. We uncover this EF-hand (MINDY3) to be a ubiquitin-binding domain with three distinct binding sites, enabling MINDY3 to bind and effectively cleave long polyubiquitin chains. Furthermore, the MINDY3 domain binds not only to polyubiquitin but also to the UBL domain of the proteasome shuttling and DNA repair factors RAD23A and RAD23B. The MINDY3 facilitates this interaction with RAD23s in cells and mediates MINDY3 recruitment to DNA damage sites, establishing this unique DUB as a potential regulator of cellular DNA damage responses. MINDY3 binds specifically to the UBL domain of RAD23s, and none of the other UBLs tested. The crystal structure of the MINDY3:RAD23A domain complex reveals the molecular basis for specificity. We find that MINDY3 can form a ternary complex with RAD23A/B and polyubiquitin, and our findings suggest a model wherein MINDY3 can deubiquitylate RAD23A/B-bound clients. - Source: PubMed
Publication date: 2026/06/09
Armstrong Lee AMcFarland Matthew RO'Dea RachelKrutyholowa RoscislawGorka MagdalenaCarroll ThomasGlatt SebastianKulathu Yogesh - Multiple myeloma (MM) remains incurable and is characterized by the abnormal proliferation of malignant plasma cells in the bone marrow. RAD23A is a multifunctional protein involved in the ubiquitin-proteasome system (UPS) and DNA damage repair; however, its role in MM remains unclear. Here, we analyzed RAD23A expression and its prognostic relevance across multiple MM cohorts. The biological functions of RAD23A in MM cells were predicted using bulk RNA-seq and single-cell RNA-seq data. Experimental validation was performed in H929 and RPMI8226 MM cell lines. Flow cytometry was used to assess cell cycle progression and apoptosis. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake assays were performed to evaluate mitochondrial respiration, glycolytic activity, and glucose uptake, respectively, and RNA sequencing was conducted to further verify the role of RAD23A in MM. Our results showed that RAD23A is upregulated in MM and that high RAD23A expression is associated with greater disease burden and more advanced disease stage. Bioinformatics analyses revealed that RAD23A high MM cells exhibited elevated metabolic activity and increased protein transport. RAD23A knockdown suppressed MM cell growth both in vitro and in vivo, induced DNA damage and endoplasmic reticulum stress, and caused G2/M cell cycle arrest and apoptosis. Moreover, RAD23A knockdown enhanced the sensitivity of MM cells to bortezomib (BTZ) and impaired mitochondrial respiration, glycolytic activity, and glucose uptake. These findings suggest that RAD23A may serve as a multifunctional regulator and potential therapeutic target in MM. - Source: PubMed
Publication date: 2026/05/04
Liu HongxiuWang YihuaLiu XunruYang NiWang SenxinZhao JieShi YaqiWang HuichaoMa Yanping - Integration of the high-risk human papillomavirus 16 (HPV16) genome into the host chromosome, frequently driven by microhomology-mediated end joining (MMEJ), is a critical step in the carcinogenesis of HPV-associated tumors. However, the mechanisms by which viral oncoproteins manipulate the error-prone MMEJ pathway remain poorly defined. Here, we demonstrate that the HPV16 E6 oncoprotein upregulates MMEJ to facilitate viral genome integration. This heightened MMEJ activity is driven by a marked increase in the protein levels of DNA polymerase theta (PolΘ), a central enzyme of the MMEJ pathway. Mechanistically, we show that the elevation of PolΘ levels in response to HPV16 E6 expression is dependent on the host E3 ubiquitin ligase UBE3A/E6AP but is independent of p53 degradation. E6 redirects UBE3A to enhance the ubiquitination and degradation of RAD23A, a shuttle protein required for delivering polyubiquitinated PolΘ to the proteasome. Consequently, the loss of functional RAD23A phenocopies the effect of HPV16 E6, leading to PolΘ protein stabilization and increased MMEJ activity. By elucidating the E6-UBE3A-RAD23A-PolΘ axis, our findings reveal a mechanism through which HPV manipulates the host DNA repair machinery to promote its integration and oncogenic potential. - Source: PubMed
Publication date: 2026/03/05
Zhu GuangliAsada ShuheiAbeykoon Jithma PSun LifangMukkavalli SirishaD'Andrea Alan D - Protein misfolding and aggregation are cardinal features of neurodegenerative disease (NDD) and they contribute to pathophysiology by both loss-of-function (LOF) and gain-of-function (GOF) mechanisms. This is well exemplified by TDP-43 which aggregates and mislocalizes in several NDDs. The depletion of nuclear TDP-43 leads to reduction in its normal function in RNA metabolism and the cytoplasmic accumulation of TDP-43 leads to aberrant protein homeostasis. A modifier screen found that loss of rad23 suppressed TDP-43 pathology in invertebrate and tissue culture models. Here we show in the TAR4 mouse model of TDP-43 pathology that genetic or antisense oligonucleotide (ASO)-mediated reduction of rad23a confers benefits on survival and behavior, histological hallmarks of disease and reduction of mislocalized and aggregated TDP-43. This results in improved function of the ubiquitin-proteasome system (UPS) and correction of transcriptomic alterations evoked by pathologic TDP-43. RAD23A-dependent remodeling of the insoluble proteome appears to be a key event driving pathology in this model. As TDP-43 pathology is prevalent in both familial and sporadic NDD, targeting RAD23A may have therapeutic potential. - Source: PubMed
Publication date: 2026/01/16
Guo XueshuiPrajapati Ravindra SinghChun JiyeonByun InsukGebis Kamil KWang Yi-ZhiLing KarenDalton CaseyBlair Jeff AHamidianjahromi AnahidBachmann GemmaRigo FrankJafar-Nejad PaymaanSavas Jeffrey NLee Min JaeSreedharan JemeenKalb Robert G - At autopsy, >95% of ALS cases display a redistribution of the essential RNA binding protein TDP-43 from the nucleus into cytoplasmic aggregates. The mislocalization and aggregation of TDP-43 is believed to be a key pathological driver in ALS. Due to its vital role in basic cellular mechanisms, direct depletion of TDP-43 is unlikely to lead to a promising therapy. Therefore, we have explored the utility of identifying genes that modify its mislocalization or aggregation. We have previously shown that loss of improves locomotor deficits in TDP-43 models of disease and increases the degradation rate of TDP-43 in cellular models. To understand the mechanism through which these protective effects occur, we generated an inducible mutant TDP-43 HEK293 cell line. We find that knockdown of reduces insoluble TDP-43 levels in this model and primary rat cortical neurons expressing human TDP-43 Utilizing a discovery-based proteomics approach, we then explored how loss of remodels the proteome. Through this proteomic screen, we identified USP13, a deubiquitinase, as a new potent modifier of TDP-43 induced aggregation and cytotoxicity. We find that knockdown of reduces the abundance of sarkosyl insoluble mTDP-43 in both our HEK293 model and primary rat neurons, reduces cell death in primary rat motor neurons, and improves locomotor deficits in ALS models. - Source: PubMed
Publication date: 2026/01/28
Dalton CaseyMojsilovic-Petrovic JelenaSafren NathanielSnoznik CarleyGebis Kamil KWang Yi-ZhiSutter Alexandra BLamitina ToddSavas Jeffrey NKalb Robert G