Ask about this productRelated genes to: AMA1 protein
- Gene:
- SKA3 NIH gene
- Name:
- spindle and kinetochore associated complex subunit 3
- Previous symbol:
- C13orf3
- Synonyms:
- MGC4832, RAMA1
- Chromosome:
- 13q12.11
- Locus Type:
- gene with protein product
- Date approved:
- 2003-01-16
- Date modifiied:
- 2016-10-05
Related products to: AMA1 protein
Related articles to: AMA1 protein
- Triple-negative breast cancer is an aggressive and heterogeneous breast cancer subtype with few effective targeted therapies and frequent resistance to chemotherapy. Here, we integrate transcriptional regulatory network inference with chromatin accessibility across a large-scale multi-system collection of primary tumors, patient-derived xenografts and model cell lines to quantify transcription factor activity and identify regulators that underpin triple-negative breast cancer identity. This approach prioritizes 94 high-confidence triple-negative breast cancer transcription factors whose activity capture inter-tumor heterogeneity and independently stratify patient outcome across clinical endpoints. Linking transcription factor activity to pharmacogenomic drug sensitivity profiles identifies reproducible drug-transcription factor associations across independent datasets, including NFE2L3 and CBFB activity as predictors of sensitivity to mTOR inhibition, which we validate in everolimus-treated triple-negative breast cancer patient-derived xenograft models. Collectively, we provide a transcriptional and chromatin-informed framework to capture triple-negative breast cancer regulatory state and expand transcription factor guided precision medicine to this breast cancer subtype. - Source: PubMed
Publication date: 2026/08/06
Bahl ShaliniDogan-Artun NergizNguyen JuliaMahmoud HassanBa-Alawi WailMadani Tonekaboni Seyed AliKang Komaldeep KaurMcGuire MeghanTobin ChantalSilvester JenniferSavage PaulCressot LucieNand AnkitaFeng GuanqiaoGuilhamon PaulMer Arvind SinghArlidge ChristopherElliott Mitchell JPark MoragCescon David WHaibe-Kains BenjaminLupien Mathieu - Drug-related UVA-induced photoreactions have been reported for several therapeutic compounds, including fluoroquinolones. CX-5461 is a clinical stage quinolone-derived anti-cancer small molecule with documented UVA-sensitizing activity. Here, we compared, by bulk and clonal whole-genome sequencing under extraneous light-protected conditions, the mutational signatures in human retinal pigment epithelial cells (RPE1) exposed to UVA, CX-5461, or co-exposed to UVA and CX-5461. Treatment with CX-5461 or UVA alone resulted in a low single-base mutation burden and background-like mutational profiles. In contrast, bulk sequencing of human cells co-exposed to UVA and CX-5461 had a markedly higher mutation burden characterized by T > A and T > C substitutions. Furthermore, single-cell clonal expansion and sequencing of CX-5461 alone, UVA alone, or CX-5461+UVA treatments confirmed that the pattern was only observed when cells were exposed to both UVA and CX-5461. The CX-5461+UVA-associated SBS signature we report arises only when CX-5461-treated cells are exposed to UVA, and is not observed when CX-5461-treated cells are shielded from light. We do not observe strong single-base mutagenic activity of CX-5461 alone, under light-protected conditions. Our data define a human SBS mutagenesis signature for CX-5461 potentiated UVA mutations and emphasize the need for appropriate controls and light-exposure precautions when studying SBS activity of known photosensitizer molecules. - Source: PubMed
Zaikova ElenaYap DamianSarvar ArmaghanHafezi AudenTan JayCerda VivianaLi KayleeLai DanielGelmon KarenHilton JohnSeymour LesleyStirling PeterCescon David WAparicio Samuel - In TROPION-Breast01 (NCT05104866), datopotamab deruxtecan (Dato-DXd) improved progression-free survival by blinded independent central review versus investigator's choice of chemotherapy (ICC) in patients with inoperable/metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer, who had disease progression on endocrine therapy and for whom endocrine therapy was unsuitable, and who had received 1-2 prior lines of chemotherapy in the inoperable/metastatic setting. We report detailed safety data and patient-reported outcomes (PROs) from the final analysis. - Source: PubMed
Publication date: 2026/07/24
Rugo H SJhaveri KPernas SPistilli BIm S-ADe Laurentiis MWang SMartínez Jañez NBorges GCescon D WHattori MLu Y-SHamilton EZhang QTsurutani JKalinsky KRubini Liedke P ENowecki ZTolaney S MZhao KAtuah KVerma DXu BBardia A - Chromosomal instability (CIN), a hallmark of malignancy, remains poorly understood in clear cell renal cell carcinoma (ccRCC). Here, we identify spindle and kinetochore-associated protein 3 (SKA3) as a critical regulator of CIN in ccRCC. BAP1 loss-of-function mutations, prevalent in ccRCC, drive aberrant SKA3 overexpression. Mechanistically, BAP1 deubiquitinates nuclear receptor co-repressor 1 (NCOR1) to enhance its recruitment to the SKA3 promoter, thereby repressing SKA3 transcription. Additionally, BAP1-mediated histone H2AK119 deubiquitination at the TRIM25 promoter activates the expression of TRIM25, facilitating ubiquitin-proteasome-mediated degradation of SKA3. BAP1 deficiency disrupts both regulatory pathways, leading to aberrant accumulation of SKA3, which fuels CIN and correlates with metastasis progression and poor prognosis. In conclusion, our findings establish dysfunction of the BAP1-SKA3 axis as a molecular driver of CIN in ccRCC and suggest SKA3 as a potential therapeutic target for BAP1-mutant ccRCC. - Source: PubMed
Publication date: 2026/07/15
Wang YueyangLai ChongWang LinglingDeng JingwenTian ZhouLiang ZhiyongZhang Honghe - The kinetochore and spindle complex (SKA) and NDC80 complexes are essential kinetochore elements that ensure highly accurate chromosome segregation and successful progression through mitosis. The SKA heterodimer complex consists of SKA1, SKA2, and SKA3 subunits, and the NDC80 complex contains NDC80, NUF2, SPC24, and SPC25 subunits. Through live cell fluorescence timelapse imaging assays and expression of RNAi-resistant SKA3 constructs, we rescue SKA complex function in cells lacking endogenous SKA3. These assays reveal a critical span within SKA3's C-terminus required for successful mitotic progression. Structural protein modeling shows that this span encompasses the majority of a roughly 40 amino acid SKA3 C-terminal structural element that promotes interaction with the coiled-coil NDC80 and NUF2 subunits of the NDC80 complex. Thus, although spindle and kinetochore concentration of the SKA complex is mediated in part by the tubulin and tip-tracking capabilities provided by the SKA1 component of the SKA complex, transition from metaphase to anaphase requires the contribution of SKA3's C-terminal structural interface to mediate interaction between the SKA and NDC80 complexes. - Source: PubMed
Publication date: 2026/05/24
Daum John RRomek NataliaGorbsky Gary J