CDC2L6 antibody Polyclonal Antibodies Primary antibodies
- Known as:
- CDC2L6 (anti-) Polyclonal Antibodies Primary antibodies
- Catalog number:
- orb100016
- Product Quantity:
- 100
- Category:
- -
- Supplier:
- Biorb
- Gene target:
- CDC2L6 antibody Polyclonal Antibodies Primary antibodies
Related genes to: CDC2L6 antibody Polyclonal Antibodies Primary antibodies
- Gene:
- CDK19 NIH gene
- Name:
- cyclin dependent kinase 19
- Previous symbol:
- CDK11, CDC2L6
- Synonyms:
- KIAA1028, bA346C16.3
- Chromosome:
- 6q21
- Locus Type:
- gene with protein product
- Date approved:
- 2003-04-15
- Date modifiied:
- 2016-06-08
Related products to: CDC2L6 antibody Polyclonal Antibodies Primary antibodies
Related articles to: CDC2L6 antibody Polyclonal Antibodies Primary antibodies
- Regulatory T (Treg) cells are pivotal in maintaining immune homeostasis through suppression of effector T (Teff) cells, making their therapeutic modulation a promising strategy for treating autoimmune and inflammatory diseases. CDK8/19 inhibitors promote Treg cell differentiation by upregulating Foxp3 expression in both naive and memory/effector T cells. In this study we identified a novel dual CDK8/19 inhibitor RO8323 and systematically dissected the mechanism of CDK8/19-mediated immunoregulation. RO8323 inhibited CDK8 and CDK19 with IC values of 2 nM and 3 nM, respectively, displaying >100-fold kinome selectivity. In the in vitro and in vivo experimental settings, we demonstrated that RO8323 selectively enhanced Treg differentiation while suppressing Teff. Furthermore, RO8323 exerted anti-inflammatory effects on myeloid cells by selectively upregulating IL-10 production but not proinflammatory cytokines (TNF-α, IL-6, and IL-12) following TLR agonist activation. In the DBA/2 → BALB/c cGVHD model, administration of RO8323 (3 mg·kg·d, i.g.) from day 7 to day 49 displayed significant therapeutic potential by reducing clinical severity scores and enhancing immune reconstitution -a finding reported for the first time in this context. Complementary studies using an ear-heart transplantation model revealed that administration of RO8323 (3, 10 mg·kg·d, i.g.) dose-dependently prolonged cardiac allograft survival accompanied by increased Treg frequencies. These results not only elucidate the immunomodulatory mechanisms of CDK8/19 inhibition but also highlight its translational value for managing alloimmune responses such as GVHD and transplant rejection. - Source: PubMed
Publication date: 2026/03/31
Shen FangXie RouGan YeRen PingWu Ran-RanYan Jia-WeiBian Yu-YingLiu Cheng-ChengYang SongHan Xin-ChunZhou Chen-GangWu YaoTang YangXu Zhi-HengYang JunQiu Hong-XiaYang Ju-HaoPu Xue-YanLi LiGui YueXia Gu-LiangLassen Kara GShen Hong CHuang Hao-ChuDai Lue - TFE3-rearranged renal cell carcinoma (TFE3-RCC) is an aggressive kidney cancer driven by oncogenic TFE3 fusion transcription factors, yet the molecular machinery that enables these fusions to reprogram transcription and drive tumor growth remains poorly defined. Here, we identify the Cyclin C-CDK8/19 Mediator kinase module as an essential co-regulator of TFE3 fusion driven transcriptional programs and tumorigenesis. Inducible expression of PRCC-TFE3 in HK-2 cells, immortalized from normal renal epithelial cells, triggered a robust oncogene-induced senescence (OIS) phenotype. Using OIS as a functional readout, we performed a genome-wide CRISPR/Cas9 loss-of-function screen and identified CCNC, encoding Cyclin C, as an essential gene required for PRCC-TFE3 activity. Genetic disruption of CCNC or pharmacologic inhibition of CDK8/19 abrogated PRCC-TFE3 induced OIS, establishing the Mediator kinase module as a critical cofactor for PRCC-TFE3 dependent transcription. Mechanistically, PRCC-TFE3 promoted nuclear accumulation of Cyclin C and their co-occupancy at genomic regions bound and transcriptionally activated by PRCC-TFE3. RNA sequencing revealed that PRCC-TFE3 induced transcriptional programs, including lysosomal, TFEB-associated, and metabolic pathways, were broadly suppressed by CDK8/19 inhibition. Importantly, while PRCC-TFE3 and Cyclin C-CDK8/19 drive OIS in non-cancerous renal epithelial cells, this same transcriptional axis exerts a context dependent pro-tumorigenic function in TFE3-RCC. In xenografts established from patient derived TFE3-RCC cell lines, genetic deletion of CCNC suppressed tumor growth, whereas in an orthotopic syngeneic TFE3-RCC mouse model, pharmacologic CDK8/19 inhibition significantly reduced tumor progression. These findings define the Mediator kinase module as a mechanistic and therapeutic vulnerability in PRCC-TFE3 driven TFE3-RCC, providing a rationale for mechanism based targeted therapy. - Source: PubMed
Publication date: 2026/03/16
Kuroda ShoichiroFunasaki ShintaroNishizawa HidekazuSchmidt Laura SKurahashi RyomaIto TakaakiArima YuichiroTanaka MiwaKitada AtsuyaJames Amy MHasumi HisashiJikuya RyosukeMakiyama KazuhideKurotaki DaisukeMinami TakashiDifilippantonio SimoneLinehan W MarstonOike YuichiSawa TomohiroTanaka YasuhitoSuda ToshioYokokawa RyujiNakamura TakuroBaba MasayaKamba Tomomi - CD4+CD25+Foxp3+ regulatory T cells (Tregs) are pivotal negative regulators of the adaptive immune system. Abnormalities in the number and/or function of Tregs contribute to the pathogenesis of primary immune thrombocytopenia (ITP). Strategies aimed at modulating Tregs offer potential therapeutic opportunities for ITP management. In this study, we demonstrated that inhibition of cyclin-dependent kinase 8 (CDK8) and CDK19 activity by the small-molecule inhibitor AS2863619 (AS) robustly promoted the conversion of CD4+CD25- effector T cells (Teffs) into CD4+CD25+Foxp3+ Tregs, endowing the converted Tregs with lineage stability and potent suppressive capacity. Mechanistically, AS rapidly augmented STAT5 phosphorylation and subsequent Foxp3 induction. STAT5 blockade completely abrogated this effect, confirming that the Treg-promoting activity of AS was critically dependent on STAT5 signaling. In parallel, AS suppressed STAT3 phosphorylation under interleukin-6-driven conditions, thereby attenuating T helper 17 (Th17) polarization. These mechanistic findings were supported by global transcriptomic analysis, which revealed a profound transcriptional shift by broadly suppressing gene programs of Teff differentiation and function while simultaneously upregulating a robust signature characteristic of stable Tregs. Crucially, unbiased upstream analysis of these changes pinpointed STAT5, STAT3, and FOXP3 as the core transcription factors mediating the drug's effect. Functional metabolic analysis further revealed that AS mediated metabolic reprogramming in T cells by suppressing glycolysis, thereby providing the necessary metabolic adaptations for Treg conversion. In a murine model of active ITP, CDK8/CDK19 inhibition elevated Treg frequencies and ameliorated thrombocytopenia in a STAT5-dependent manner. Collectively, our study highlighted the therapeutic potential of CDK8/CDK19 inhibition in restoring immune homeostasis and managing ITP. - Source: PubMed
Wang Yan-MingZhou HuLeng Shao-QiuMa Jun-JieLi Hui-YuanLi Guo-ShengSun TaoXu Yi-TongHan Shou-QingGu Yu-FengDong LinYan Zhen-YuZhang LeiPeng JunLiu Xin-Guang - Hepatitis delta virus (HDV) is a satellite virus of the hepatitis B virus (HBV), with a single-stranded and rod-like circular RNA encoding only one protein, the hepatitis delta antigen (HDAg). Lacking its own replicase, the highly self-complementary HDV RNA hijacks host RNA polymerase II (Pol-II), eliciting a unique and incompletely understood RNA-templated transcriptional activity. Because transcription by Pol-II is regulated at multiple steps by various cyclin-dependent kinases (CDKs), we investigated whether CDKs contribute to HDV replication. - Source: PubMed
Publication date: 2026/02/10
Prawira AnggaHilleke MattisChen MengqianRoninson Igor BBartenschlager RalfUrban StephanNi Yi - CDK8/19 are transcriptional cyclin dependent kinases, which do not directly control cell cycle progression. CDK8/19 are involved in regulation of multiple processes in embryogenesis, cancer progression, immune activation and others. Previously we demonstrated that CDK8/19 are critical for spermatogenesis in mice. Here we report that CDK8/19 activity is also required for oocyte maturation playing a significant role in meiosis resumption in mouse oocytes. Two chemically distinct CDK8/19 inhibitors - Senexin B and Snx631 prevented nuclear envelope breakdown and first polar body extrusion, blocking key molecular events required for exiting the dictyate - inhibition of PKA activity and activation of the CDK1/Cyclin B complex. This effect did not cause cytotoxicity, and oocytes could resume progression upon transfer into fresh media. Inhibition of CDK8/19 also prevented meiotic-specific mitochondrial expansion and clustering. Notably, these effects appear to be independent of roles of CDK8/19 in transcription, which is not required for resumption of meiosis. These findings for the first time demonstrate the roles of CDK8/19 activity in oocyte maturation, through its role in transcription-independent regulation of PKA activity. - Source: PubMed
Publication date: 2026/01/17
Okulova YuliaFilatov MaximVarlamova EkaterinaTvorogova AnnaKorshunov EvgeniySilaeva YuliaTatarskiy VictorBruter Alexandra