Ask about this productRelated genes to: Cdk7 antibody
- Gene:
- CDK7 NIH gene
- Name:
- cyclin dependent kinase 7
- Previous symbol:
- -
- Synonyms:
- CAK1, CDKN7, MO15, STK1, CAK
- Chromosome:
- 5q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1994-12-16
- Date modifiied:
- 2016-10-05
Related products to: Cdk7 antibody
Related articles to: Cdk7 antibody
- FUS and EWSR1 are RNA-binding proteins that accumulate at DNA lesions in a poly(ADP-ribose)-dependent manner. Notably, upon foci formation, both proteins are gradually excluded from sites of complex DNA damage, yet the mechanism and significance of this exclusion remain unclear. Here, we show that inhibition of the transcription-associated cyclin-dependent kinases CDK7, CDK9, and CDK12/13, or degron-mediated depletion of RPB1, the catalytic subunit of RNA polymerase II, prevents the exclusion of FUS and EWSR1. RPB1 itself is also excluded from sites of DNA damage with kinetics similar to those of FUS. Furthermore, we demonstrate that CDK7 inhibition leads to reduced 53BP1 accumulation at DNA lesions in vivo. Our findings clarify a mechanism by which RPB1 and FUS/EWSR1 are excluded from damaged chromatin and highlight its importance in DNA repair coordination. - Source: PubMed
Publication date: 2026/04/08
Varhoshkova SylviaSang Christopher ChinAntonova LianaUzunova SonyaKirova DilyanaAleksandrov RadoslavKanemaki Masato TLee Hyun OStoynov Stoyno - HER2-positive/hormone-receptor-positive breast cancer represents approximately 10% of all breast cancer cases and constitutes a distinct biological entity with unique therapeutic challenges. The complex crosstalk between HER2 and estrogen receptor signaling pathways contributes to both primary and acquired resistance to anti-HER2 therapies, and the convergence of these pathways on cell cycle regulation, particularly through the cyclin D1-CDK4/6-Rb axis, has provided a compelling rationale for combining CDK4/6 inhibitors with anti-HER2 therapy. This scoping review aimed to map preclinical and clinical evidence evaluating combinations of CDK4/6 inhibitors with HER2-targeted therapy in HER2+/HR+ disease. Eligible sources included preclinical models and clinical studies assessing CDK4/6 inhibitor-based combinations with anti-HER2 therapy, identified through searches of PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov. Data were charted and synthesized descriptively according to PRISMA-ScR guidelines. Preclinical studies have demonstrated synergistic antitumor activity when CDK4/6 inhibitors are combined with trastuzumab, pertuzumab, or newer HER2-targeted agents across multiple HER2+ breast cancer models. In the metastatic setting, phase II trials including MonarcHER and PATRICIA II have shown encouraging efficacy signals, while the phase III PATINA trial demonstrated a clinically meaningful 15.2-month progression-free survival benefit with palbociclib plus anti-HER2 therapy and endocrine therapy. In the neoadjuvant setting, trials including NA-PHER2 and MUKDEN-01 demonstrated marked Ki67 suppression and promising pathologic responses, supporting the exploration of chemotherapy de-escalation strategies. Despite these advances, key challenges remain including the identification of predictive biomarkers, optimal treatment sequencing, and the integration of emerging HER2-targeted agents such as trastuzumab deruxtecan. Novel CDK4/6 inhibitors including dalpiciclib and next-generation agents are expanding therapeutic options, while combination strategies incorporating CDK7 inhibition represent future therapeutic frontiers. The evolving landscape of HER2+/HR+ breast cancer treatment increasingly emphasizes precision medicine approaches that leverage cell cycle control mechanisms to overcome resistance and improve patient outcomes across all disease stages. - Source: PubMed
Publication date: 2026/03/03
Poli IlariaOliva Gaia RacheleMongelli GinevraRotondi AngelachiaraFrescura ValentinaArcuri GiorgiaGarufi GiovannaPontolillo LetiziaMastrantoni LucaDi Monte ElenaMaliziola NoemiFucile Maria AntoniaSalvatori FrancescaMondello RitaPalazzo AntonellaFabi AlessandraBria EmilioTortora GiampaoloOrlandi Armando - Glioblastomas are the most prevalent and aggressive malignant brain tumors, characterized by hypertranscription and dependence on neurodevelopmental transcription factors. The transcriptional cycle is regulated by phosphorylation of the C-terminal domain (CTD) of RNA polymerase II (RNAPII) by transcriptional cyclin-dependent kinases (tCDKs), including CDK7, CDK9, CDK12, and CDK13. Here we find that glioblastoma stem cells (GSCs) are selectively sensitive to CDK12/CDK13 inhibition, whereas CDK7 and CDK9 inhibition cause non-specific cytotoxicity. This selective targeting halts GSC and organoid proliferation, curtails GSC invasion and suppresses tumor growth in a xenograft mouse model. In GSCs, CDK12/CDK13 inhibition leads to a rapid and genome-wide loss of serine-2 phosphorylation (pSer2) of the RNAPII CTD, abolishing transcriptional elongation and a transcriptional program sustained by key neurodevelopmental transcription factors. CDK12/CDK13 inhibition unexpectedly arrests DNA replication and replication fork progression in a manner distinct from the effect of inhibiting other tCDKs. This dramatic arrest precedes DNA damage response activation and cell cycle arrest, directly linking RNAPII elongation to replication fork dynamics and revealing a previously unrecognized dependence of DNA replication on CDK12/CDK13-RNAPII regulation. - Source: PubMed
Publication date: 2026/03/25
Lier SiljeMarkusson Sara BKocijancic AnjaNarum MartineLund Solveig OBöllering BiankaLipsa AnujaSøegaard Mirra L CRein Idun DSantha PetraJain PreetiLång AnnaLång EmmaMeyer NiklasDutta AparajitaAnand SantoshBadugu Sugith BNesse Gaute JForstrøm Rune JKlungland ArneAnand AshishPollard Steven MBøe Stig ORinholm Johanne EFrauenknecht Katrin B MGolebiewska AnnaNiclou Simone PSomyajit KumarLerdrup MadsPandey Deo P - Cyclin-dependent kinase 7 (CDK7), a key regulator of cell cycle progression and transcriptional control, has emerged as a promising therapeutic target in acute leukemia. While CDK7 inhibitors have shown antileukemic activity, their clinical utility is often restricted by dose-dependent thrombocytopenia. To overcome this challenge, we developed and characterized a series of CDK7-selective PROTAC degraders. By engaging the VHL E3 ligase, which is minimally expressed in platelets, CXJ2080 achieves tumor-selective CDK7 degradation with remarkable potency and selectivity (a DC of 0.88 nM and >98% degradation efficiency). This selective targeting spares platelets, thereby avoiding the hematologic toxicity associated with conventional CDK7 inhibitors. Mechanistically, CDK7 degradation disrupts the CDK7-cyclin H-MAT1 complex, simultaneously suppressing MYC-driven oncogenic signaling while activating the p53-p21 tumor suppressor axis. These effects have culminated in robust antileukemic activity in preclinical models, while preserving normal peripheral blood mononuclear cell (PBMC) function. Collectively, our findings establish CXJ2080 as a next-generation CDK7-targeted therapeutic agent with enhanced efficacy and reduced hematotoxicity, showing great promise for the treatment of acute leukemia. - Source: PubMed
Publication date: 2026/03/25
Tu YutongCai XiaojiaTao ZhaofanZhang RuisenLi XianChen BeijingZhang HualinHu XiaobeiKe JiayiChen XiaoyaBai XinyanLi JiaXu TianfengZhou Yubo - Overcoming tumor thermotolerance within clinically safe temperature ranges remains a central limitation of photothermal therapy (PTT). Here we report a closed-loop therapeutic nanoplatform that integrates topologically enhanced photothermal conversion with thermally gated CRISPR/Cas9 regulation. Rationally engineered hexagonal bismuthene nanodiscs exhibit strong near-infrared responsiveness, enabling mild hyperthermia (∼45 °C) that activates a heat-sensitive CRISPR switch targeting CDK7. The resulting disruption of the CDK7-HSP70 stress axis lowers the thermal resistance threshold and reprograms tumor adaptation, thereby amplifying photothermal efficacy and promoting immunogenic cell death. In triple-negative breast cancer models, this gene-thermal feedback achieves >93% tumor inhibition with minimal systemic toxicity. This work establishes a genetically programmable, thermogenetic nanomaterial paradigm that links material design with gene logic for next-generation precision cancer therapy. - Source: PubMed
Publication date: 2026/03/03
Chen ZhiLin HuilingYoon ChangyuHuang HaoKim YujinMeng ChangleJang HoyeonXie ZhongjianLi LinjunLiu YingxiaKim Jong SeungZhang Han