Ask about this productRelated genes to: DDX21 Blocking Peptide
- Gene:
- DDX21 NIH gene
- Name:
- DExD-box helicase 21
- Previous symbol:
- -
- Synonyms:
- RH-II/GU, GURDB
- Chromosome:
- 10q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-12-15
- Date modifiied:
- 2016-10-05
Related products to: DDX21 Blocking Peptide
Related articles to: DDX21 Blocking Peptide
- Cellular dormancy in colorectal cancer (CRC) significantly contributes to therapeutic resistance, tumor recurrence, and metastasis, resulting in poor prognosis. However, the underlying molecular mechanisms remain poorly understood. Here, we used spheroid culture combined with serum deprivation to enrich and identify dormancy-like CRC cells in vitro and characterized their dormancy-like phenotype by G0/G1 phase arrest, suppressed proliferation and radio-resistance. Compared to proliferative cells, dormancy-like CRC cells maintained similar tumor formation capacity but displayed higher PD-L1 expression level and enhanced migratory ability, indicating greater aggressiveness. Proteomics analysis revealed DDX21 was significantly downregulated in dormancy-like CRC cells, and analysis of clinical data showed an inverse correlation between DDX21 and PD-L1 in CRC patients. This is consistent with the findings that knocking down DDX21 markedly increased PD-L1 levels, suggesting a role for DDX21 in immune evasion. Importantly, overexpressing DDX21 reversed the radio-resistance of dormancy-like CRC cells. Mechanistically, DDX21 downregulation induced a dormancy-like phenotype via p38MAPK activation and AKT suppression to inhibit cellular growth. Furthermore, DDX21 bound to the NUCKS1 promoter, and its downregulation reduced NUCKS1 transcription, leading to elevated p27/p21 levels, which reinforced G0/G1 arrest. We also identified HERC2 as the E3 ligase mediating DDX21 degradation via K48/K63-linked polyubiquitination, dependent on the DDX21 helicase core domain. In conclusion, our findings establish DDX21 as a crucial regulator of dormancy-like phenotype in colorectal cancer cells and highlight its potential as a biomarker for dormancy-like tumor populations, radioresistance and poor clinical outcomes in CRC. - Source: PubMed
Publication date: 2026/05/03
Xiao YuqiHe MingyuanYao HanSong YimengHu YuLiu XinglongBai YangZhang JianghongShao ChunlinPan Yan - Bisphenol A (BPA) is a prevalent chemical used in the production of plastics. While adverse effects on the reproductive system have been documented, more recent studies also associated BPA exposure with carcinogenesis as well as genomic instability. However, these studies were generally performed using BPA concentrations much higher than those observed in the serum or urine of the general population, making their relevance unclear. To address this, we report here an unbiased genetic study to identify mechanisms responding to environmentally relevant BPA exposure. We performed genome-wide CRISPR knockout screens in HeLa and RPE1 cells upon continuous exposure to 0.5uM BPA, a concentration similar to the mean BPA concentration found in the urine of plastics manufacturing workers, for 19 days. We found genome stability genes among the top common hits between the two cell lines, suggesting that BPA causes DNA damage at this environmentally relevant exposure dose. We validated the DNA repair gene RAD51C and the RNA helicase DDX21 as genes required for BPA resistance. Moreover, we show that BPA exposure increases the formation of R-loops which are resolved by DDX21. Our study suggests that BPA exposure at environmentally relevant doses can cause DNA damage, highlighting the relevance of BPA for carcinogenesis. - Source: PubMed
Publication date: 2026/04/15
Hale AnastasiaNusawardhana AlexandraStraka JoshuaNicolae Claudia MMoldovan George-Lucian - Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with low immunotherapy efficacy due to an immunosuppressive tumor microenvironment in proficient mismatch repair (pMMR) disease, which accounts for most cases of CRC. Herine, we have identified discoidin domain receptor 1 (DDR1) as a key immune evasion driver in syngeneic tumor models. Moreover, intestine-specific Ddr1 knockout suppressed tumorigenesis in AOM/DSS and ApcMin/+ mouse models of CRC, with reduced frequency of M2-like tumor-associated macrophages (TAMs) and increased infiltration of CD8+ T cells. Mechanistically, DDR1 induced p-c-Jun-dependent IL33 transcription to drive M2-like macrophage polarization. Mass spectrometry and immunoprecipitation analyses further revealed that DDR1 interacted with DExD-Box Helicase 21 (DDX21) in the nucleus, which inhibited DDX21 ubiquitination, increasing DDX21 levels, which subsequently enhanced c-Jun phosphorylation. Clinically, elevated DDR1 expression in CRC patients correlated with poor prognosis and was positively associated with DDX21 and p-c-Jun. Furthermore, both DDR1 and DDX21 expression showed positive correlations with M2-like TAM infiltration in patient tissues. Therapeutically, genetic knockout and nanoparticle-delivered siRNA targeting DDR1 significantly enhanced anti-PD-1 treatment efficacy in vivo. Thus, our findings establish DDR1-DDX21-c-Jun-IL-33 as an axis that drives immunosuppression in CRC by regulating TAM polarization and indicate DDR1 as a potential target to improve immunotherapy efficacy in pMMR patients. - Source: PubMed
Publication date: 2026/04/10
Duan XiaofanYeerkenbieke GaoshaerFeng YanjunZhou MingwangZhang YumeiZhou JiuliLi Jin - The nucleocapsid (N) protein of SARS-CoV-2 is essential for viral replication and transcription, in part through interactions with host proteins. Here, we delineate distinct mechanisms underlying N protein association with human RNA helicases DDX1 and DDX21. Co-immunoprecipitation assays in HEK293 cells modified to express N protein revealed that DDX1 binding requires the N protein serine-arginine (SR) region, as SR deletion markedly reduced interaction. Inhibition of glycogen synthase kinase-3 (GSK-3), which targets the SR region, serine-to-alanine substitutions within the SR region, and alkaline phosphatase treatment of extract, respectively, demonstrated that phosphorylation of the SR region is critical for DDX1 binding. Furthermore, phosphorylated or phospho-mimetic SR peptides both prevented N protein-DDX1 complex formation and disrupted preformed complexes in vitro, whereas unphosphorylated peptides had no effect, confirming a phosphorylation-dependent binding mechanism. In contrast, interaction with DDX21 was unaffected by SR deletion or phosphorylation status and required both the N- and C-terminal domains of the N protein. RNase treatment enhanced N-DDX21 association without altering N-DDX1 interactions, indicating distinct regulation by RNA. Domain mapping of the two helicases identified the DDX1 N-terminal and the DDX21 C-terminal domains as interfaces that bind the N protein. Together, these findings support phosphorylation-dependent recruitment of DDX1 versus phosphorylation-independent engagement of DDX21, highlighting mechanistically distinct strategies by which SARS-CoV-2 N co-opts host helicases. - Source: PubMed
Publication date: 2026/03/26
Wang LiangjunBaxley Ryan MLargaespada David AAihara HidekiBielinsky Anja Katrin - The coexistence of and ( promoter alterations has been reported to cooperatively upregulate TERT expression and is well recognized as a biomarker for aggressive thyroid cancer. However, the mechanism underlying their synergistic effect remains elusive. - Source: PubMed
Publication date: 2026/01/22
Chen MengkeJiang KeZhang QiXiao XiZhu LefanSang YeHu GuanghuiYu ShuangHong ShubinLv WeimingXiao HaipengLiu Rengyun