Ask about this productRelated genes to: CCND1 Blocking Peptide
- Gene:
- CCND1 NIH gene
- Name:
- cyclin D1
- Previous symbol:
- BCL1, D11S287E, PRAD1
- Synonyms:
- U21B31
- Chromosome:
- 11q13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1991-06-06
- Date modifiied:
- 2019-04-23
Related products to: CCND1 Blocking Peptide
Related articles to: CCND1 Blocking Peptide
- Uncontrolled cell cycle progression is a hallmark of cancer, tightly regulated by both intrinsic and extrinsic stimuli. However, the role of fatty acids, in particular palmitic acid, in cell cycle control remains incompletely understood. Here, we observe that inhibition of protein palmitoylation by administrating 2-bromohexadecanoic acid (2-BP) or depleting ZDHHC17, leads to profound cell cycle arrest. Mechanistically, ZDHHC17 palmitoylates CDK4, thereby facilitating its interaction with cyclin D1 (encoded by CCND1), a process depending on TRAF6-mediated K11-linked ubiquitination of CDK4. While, blockade of either palmitoylation or ubiquitination markedly reduces CDK4 kinase activity, resulting in cell cycle arrest and suppressed tumor growth. Furthermore, Zdhhc17-depletion displays reduced cell cycle progression and immune response in a high fat diet (HFD)-feeding mouse model. Clinically, high ZDHHC17 expression is positively correlated with non-response to anti-PD-1 therapies in cancer patients, partially due to CDK4-mediated repression of PD-L1. Thereby, we propose a rational combination strategy of employing CDK4 inhibitors with immune checkpoint blockers (ICBs) to overcome ZDHHC17-driven cancers. In sum, our study uncovers a novel cell cycle control mechanism by ZDHHC17-mediated palmitoylation and TRAF6-mediated ubiquitination of CDK4, presenting a potential therapeutic avenue by targeting the ZDHHC17-TRAF6-CDK4 axis for cell cycle dysregulated cancers. - Source: PubMed
Publication date: 2026/05/14
Wang ZekangSong PeipeiWu XuejiWang LeiXie WeiFeng PinningCheng ChaoGuo Jianping - Acute lymphoblastic leukemia (ALL) is a clinically diverse cancer in which microRNA (miRNA)-mediated post-transcriptional regulation contributes to leukemogenesis and subtype heterogeneity. In this study, miRNA expression profiling by microarray was performed on ALL cases (B-ALL and T-ALL) and healthy controls. Data were normalized and analyzed for differential expression using false discovery rate (FDR)-adjusted -values. Differentially expressed miRNAs were further examined using unsupervised visualization to assess overall disease-related expression patterns. To explore their biological significance, experimentally validated miRNA-target interactions were obtained using multiMiR, limited to validated databases (miRTarBase, TarBase, and miRecords) and summarized via target-burden ranking, miRNA-target network analysis, and Circos-style interaction mapping. A unique miRNA expression signature was identified in ALL. Upregulated miRNAs included miR-106a-5p, miR-106b-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-181b-5p, and miR-128-3p, while miR-127-3p, miR-139-5p, miR-433-3p, and miR-584-5p were downregulated. Validated targets concentrated on key leukemia-related genes like PTEN, BCL2L11, CDKN1A, CCND1, RB1, E2F1, and TGFBR2. KEGG pathway analysis highlighted pathways associated with leukemic cell survival and growth, including MAPK, cell cycle, autophagy, Hippo, ubiquitin-mediated proteolysis, and mTOR signaling pathways. These findings reveal a concise ALL-associated miRNA panel predominantly comprising the miR-17/20/106 family and provide a prioritized set of candidate regulatory networks for subtype-specific validation and functional follow-up studies. - Source: PubMed
Publication date: 2026/04/27
Basingab Fatemah SAlahdal HadilAlwadaani DeemahAlmuneef GhaidaBarefah Ahmed SAlgiraigri Ali HHammad RawanElnakeeb MohamedAlrahimi Jehan SZaher Kawther AAldahlawi Alia M - Tongue squamous cell carcinoma (TSCC) is an aggressive malignancy with poor prognosis and limited therapeutic options. Herbal medicines with multitarget activities and low toxicity have attracted increasing attention in cancer adjuvant therapy. This study aimed to investigate the anti-tumor effects and underlying mechanisms of the water extract of (APW) in TSCC in vitro and in vivo. Two TSCC cell lines, Cal-27 and SCC25, were used for cell-based functional and mechanistic studies, while a Cal-27 xenograft-bearing mouse model was established for evaluating the in vivo effect of APW treatment. Our results showed that APW could significantly inhibit the proliferation of Cal-27 and SCC25 cells and induce apoptosis in a concentration-dependent manner. APW could promote mitochondrial-mediated apoptosis by upregulating Bax and cleaved caspase proteins but downregulating Bcl-2 in TSCC cells. It also suppressed the Wnt/β-catenin signaling pathway, reducing β-catenin expression and its downstream targets, CCND1, MYC, and JUN. Furthermore, APW disrupted mitochondrial integrity, induced cytochrome c release, and reduced mitochondrial membrane potential. APW also inhibited epithelial-mesenchymal transition, increasing E-cadherin and decreasing N-cadherin and vimentin expressions, thereby suppressing cell migration of TSCC cells. Furthermore, the 5-week APW treatment significantly reduced tumor growth and angiogenesis without evident hepatic or renal toxicity in Cal-27 xenograft-bearing mice. In conclusion, APW exerted potent anti-tumor effects by targeting both the Wnt/β-catenin pathway and mitochondrial apoptotic machinery, suggesting the great potential of APW as an adjuvant therapeutic candidate for TSCC treatment. - Source: PubMed
Publication date: 2026/04/23
Yue Grace Gar-LeeHuang JingyiLu XiaotongLee Julia Kin-MingGao SiChan Jason Ying KuenLau Clara Bik-San - Vulvar squamous cell carcinoma (VSCC) comprises biologically distinct subtypes with divergent molecular profiles and clinical behaviors. In this study, we performed comprehensive genomic profiling of 48 primary VSCCs, integrating mutational and copy number data with HPV status and clinicopathological parameters. Tumors were stratified into HPV-associated (HPVA), HPV-independent (HPVI), and a third proposed subgroup characterized by HPV negativity and wild-type TP53 status. Overall, 650 somatic mutations were identified, with TP53, TERT promoter, NOTCH1, PIK3CA, and CDKN2A being the most frequently altered genes. HPVA VSCCs exhibited a higher mutational burden and enrichment of PIK3CA, NOTCH1, and MLL2 mutations, consistent with APOBEC-driven mutagenesis. HPVI VSCCs showed frequent TP53, TERTp, and CDKN2A mutations, along with an age-related mutational signature. Copy number alterations were more common in HPVI tumors, with recurrent amplifications in CCND1, FGF3/4/19, and CDK pathway genes. Six VSCCs lacked both HPV association and TP53 mutations, supporting the existence of a third molecular subtype, with frequent TERTp mutations and limited additional alterations. No significant survival differences were observed between subtypes, although nodal status remained prognostically relevant. These findings refine the molecular taxonomy of VSCC, support the recognition of a third genomic subgroup, and highlight subtype-specific therapeutic targets. - Source: PubMed
Publication date: 2026/05/11
Choschzick MHoesli LStergiou CRüschoff J H - Dopaminylation, the covalent attachment of dopamine to the side chain of glutamine in proteins, represents a newly characterized class of posttranslational modifications. Because of the limited identification of substrates, the functions and molecular mechanisms associated with dopaminylation remain largely uncharacterized. Using an alkyne-functionalized dopamine probe, we developed a method for selectively enriching dopaminylated proteins in whole-cell systems. This approach provided a comprehensive resource of 4,133 dopamine-enriched protein candidates and peptide-level analysis with acid-cleavable tags identified 1,181 putative dopaminylated proteins, including histone H4 dopaminylation at Q27 (H4Q27dop), which we further validated. Functionally, H4Q27dop acts as a transcriptional repressor in a neuroblastoma model, where it blocks CEBPD binding at the CCND1 promoter, leading to transcriptional downregulation of CCND1 and subsequent suppression of cell proliferation. Our findings provide both a valuable resource of dopaminylated substrate proteins and a distinct mechanistic insight into how dopamine regulates neuroblastoma cell growth. - Source: PubMed
Publication date: 2026/05/08
Zhang YinfengYang YaqiWu WenyanZhang MinRao JiananSong WentingPan YiShen NanLi LinxueMin TaishanLi KaiZhang XiaoqingQiu Xin-YueZhang Shu-YuYang WenjunZang JianyeLiu YuMo Xi