Ask about this productRelated genes to: CAPN7 antibody
- Gene:
- CAPN7 NIH gene
- Name:
- calpain 7
- Previous symbol:
- -
- Synonyms:
- PalBH
- Chromosome:
- 3p25.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-12-02
- Date modifiied:
- 2016-10-05
Related products to: CAPN7 antibody
Related articles to: CAPN7 antibody
- CDK12 and CDK13, two transcriptional cyclin-dependent kinases (CDKs), are emerging as therapeutic targets in epithelial cancers due to their vital roles in transcriptional elongation and maintaining genomic stability. However, the absence of predictive biomarkers may impede the clinical use of CDK12/13 inhibitors. Here, we identify CDK10 as a consistent and kinase-dependent regulator of sensitivity to CDK12/13 inhibition. A genome-wide CRISPR-Cas9 screen across six breast and ovarian cancer models reveals CDK10 loss as a top-ranked enhancer of response to the selective CDK12/13 inhibitor CTX-439. Functional validation in multiple cancer cell lines and xenograft models shows that CDK10 deficiency boosts apoptotic responses and increases the antitumor effects of CDK12/13 inhibition. Mechanistically, CDK10 loss extends the duration of CTX-439-induced transcriptional suppression and delays RNA polymerase II re-engagement at sensitive gene loci, exemplified by CAPN7 and SENP6. These findings indicate CDK10 as a probable biomarker for patient stratification and as a co-target to boost the efficacy of transcriptional therapies. Our work reveals a previously underappreciated role for CDK10 in transcriptional resilience, emphasizing its potential to guide and enhance CDK12/13-based cancer treatments. - Source: PubMed
Publication date: 2026/06/11
Islam ShafiqulTarumoto YusukeTakano MarikoSugino SeiichiNishibuchi GoheiMizutani AkioYamakawa HirokoMorishita DaisukeYusa Kosuke - The Endosomal Sorting Complexes Required for Transport (ESCRT) machinery mediates the membrane fission step that completes cytokinetic abscission and separates dividing cells. Filaments composed of ESCRT-III subunits constrict membranes of the intercellular bridge midbody to the abscission point. These filaments also bind and recruit cofactors whose activities help execute abscission and/or delay abscission timing in response to mitotic errors via the NoCut/Abscission checkpoint. We previously showed that the ESCRT-III subunit IST1 binds the cysteine protease Calpain-7 (CAPN7) and that CAPN7 is required for both efficient abscission and NoCut checkpoint maintenance (Wenzel et al., 2022). Here, we report biochemical and crystallographic studies showing that the tandem microtubule-interacting and trafficking (MIT) domains of CAPN7 bind simultaneously to two distinct IST1 MIT interaction motifs. Structure-guided point mutations in either CAPN7 MIT domain disrupted IST1 binding in vitro and in cells, and depletion/rescue experiments showed that the CAPN7-IST1 interaction is required for (1) CAPN7 recruitment to midbodies, (2) efficient abscission, and (3) NoCut checkpoint arrest. CAPN7 proteolytic activity is also required for abscission and checkpoint maintenance. Hence, IST1 recruits CAPN7 to midbodies, where its proteolytic activity is required to regulate and complete abscission. - Source: PubMed
Publication date: 2023/09/29
Paine Elliott LSkalicky Jack JWhitby Frank GMackay Douglas RUllman Katharine SHill Christopher PSundquist Wesley I - Testicular germ cell tumor (TGCT) is the most common tumor in young men, but molecular signatures, especially the alternative splicing (AS) between its subtypes have not yet been explored. - Source: PubMed
Publication date: 2023/01/13
Yao XiangyangZhou HuiDuan ChenWu XiaoliangLi BoLiu HaoranZhang Yangjun - Merino sheep are a breed of choice across the world, popularly kept for their wool and mutton value. They are often reared as a pure breed or used in crossbreeding and are a common component in synthetic breed development. This study evaluated genetic diversity, population structure, and breed divergence in 279 animals of Merino and Merino-based sheep breeds in South Africa using the Illumina Ovine SNP 50K BeadChip. The sheep breeds analysed included the three Merino-derived breeds of Dohne Merino ( = 50); Meatmaster ( = 47); and Afrino ( = 52) and five presumed ancestral populations of Merinos (Merino ( = 46); South African Merino ( = 10); and South African Mutton Merino ( = 8)); and the non-Merino founding breeds of Damara ( = 20); Ronderib Afrikaner ( = 17); and Nguni ( = 29). Highest genetic diversity values were observed in the Dohne Merino (DM), with = 0.39 ± 0.01, followed by the Meatmaster and South African Merino (SAM), with = 0.37 ± 0.03. The level of inbreeding ranged from 0.0 ± 0.02 (DM) to 0.27 ± 0.05 (Nguni). Analysis of molecular variance (AMOVA) showed high within-population variance (>80%) across all population categories. The first principal component (PC1) separated the Merino, South African Mutton Merino (SAMM), DM, and Afrino (AFR) from the Meatmaster, Damara, Nguni, and Ronderib Afrikaner (RDA). PC2 aligned each Merino-derived breed with its presumed ancestors and separated the SAMM from the Merino and SAM. The analysis yielded selection sweeps across the AFR (12 sweeps), Meatmaster (four sweeps), and DM (29 sweeps). Hair/wool trait genes such as ; metabolic genes of , , ; and immune response genes of , , , and were reported. Other genes include , which was observed as selection signatures in other populations; , important in the development of the skeleton and mammary glands; , associated with adaptation to variation in climatic conditions; and , which has been reported as strongly selected in both fat-tailed and thin-tailed sheep. The DM vs. SAMM shared all six sweep regions on chromosomes 1, 10, and 11 with AFR vs. SAMM. Genes such as on OAR 1:191.3-194.7 Mb and on OAR 11:28.6-31.3 Mb were observed. The selection sweep on chromosome 10 region 28.6-30.3 Mb harbouring the for polledness was shared between the DM vs. Merino, the Meatmaster vs. Merino, and the Meatmaster vs. Nguni. The DM vs. Merino and the Meatmaster vs. Merino also shared an Rsb-based selection sweep on chromosome 1 region 268.5-269.9 Mb associated with the gene, The study demonstrated some genetic similarities between the Merino and Merino-derived breeds emanating from common founding populations and some divergence driven by breed-specific selection goals. Overall, information regarding the evolution of these composite breeds from their founding population will guide future breed improvement programs and management and conservation efforts. - Source: PubMed
Publication date: 2023/01/04
Dzomba E FVan Der Nest M AMthembu J N TSoma PSnyman M AChimonyo MMuchadeyi F C - The 12 related human ESCRT-III proteins form filaments that constrict membranes and mediate fission, including during cytokinetic abscission. The C-terminal tails of polymerized ESCRT-III subunits also bind proteins that contain Microtubule-Interacting and Trafficking (MIT) domains. MIT domains can interact with ESCRT-III tails in many different ways to create a complex binding code that is used to recruit essential cofactors to sites of ESCRT activity. Here, we have comprehensively and quantitatively mapped the interactions between all known ESCRT-III tails and 19 recombinant human MIT domains. We measured 228 pairwise interactions, quantified 60 positive interactions, and discovered 18 previously unreported interactions. We also report the crystal structure of the SPASTIN MIT domain in complex with the IST1 C-terminal tail. Three MIT enzymes were studied in detail and shown to: (1) localize to cytokinetic midbody membrane bridges through interactions with their specific ESCRT-III binding partners (SPASTIN-IST1, KATNA1-CHMP3, and CAPN7-IST1), (2) function in abscission (SPASTIN, KATNA1, and CAPN7), and (3) function in the 'NoCut' abscission checkpoint (SPASTIN and CAPN7). Our studies define the human MIT-ESCRT-III interactome, identify new factors and activities required for cytokinetic abscission and its regulation, and provide a platform for analyzing ESCRT-III and MIT cofactor interactions in all ESCRT-mediated processes. - Source: PubMed
Publication date: 2022/09/15
Wenzel Dawn MMackay Douglas RSkalicky Jack JPaine Elliott LMiller Matthew SUllman Katharine SSundquist Wesley I