Ask about this productRelated genes to: FOXM1 Blocking Peptide
- Gene:
- FOXM1 NIH gene
- Name:
- forkhead box M1
- Previous symbol:
- FKHL16
- Synonyms:
- HFH-11, trident, HNF-3, INS-1, MPP2, MPHOSPH2, TGT3
- Chromosome:
- 12p13.33
- Locus Type:
- gene with protein product
- Date approved:
- 1997-07-25
- Date modifiied:
- 2016-10-05
Related products to: FOXM1 Blocking Peptide
Related articles to: FOXM1 Blocking Peptide
- USP5 is a deubiquitinating enzyme whose role in anti-PD-L1 resistance in breast cancer remains unclear. This study investigated whether USP5 contributes to resistance against the anti‑PD‑L1 antibody (atezolizumab) by regulating the FOXM1/Nectin2 axis. Anti-PD-L1-resistant and lung metastatic mouse models were established, combined with in vitro cellular assays, clinical sample analyses, and bioinformatics approaches. The results showed that USP5 was upregulated in breast cancer and stabilized FOXM1 via deubiquitination, which led to increased Nectin2 expression and resistance to CD8⁺ T cell-mediated killing. Knockdown of USP5 or its pharmacological inhibition with G9 synergized with anti-PD-L1 to suppress tumor growth, an effect that was reversible by Nectin2 overexpression. In conclusion, USP5 promotes breast cancer progression and anti-PD-L1 resistance by deubiquitinating FOXM1, thereby upregulating Nectin2 expression. Targeting USP5 enhances the efficacy of anti-PD-L1 therapy, offering a novel strategy to overcome immunotherapy resistance in breast cancer. - Source: PubMed
Publication date: 2026/09/22
Li GuangyanSu ZhiyuanZhang YutongDu QiguangXu ZhongkaiCui HeZhang Jianguo - Primitive hematopoietic stem cells (pHSCs) sustain lifelong hematopoiesis through tightly regulated transitions between quiescence and activation. Circadian oscillations influence hematopoiesis; however, the mechanisms coordinating metabolic state and stem cell function daily remain incompletely defined. Here, we show that circadian cues coordinated a program of mitochondrial remodeling, metabolic reprogramming, and structural adaptation in pHSCs. At night, peak melatonin levels were associated with reduced mitochondrial membrane potential, increased mitochondrial reactive oxygen species, and activation of DRP1 and PINK1 dependent mitophagy, resulting in enhanced long term repopulating capacity. In parallel, pHSCs exhibited increased glycolytic activity characterized by elevated glucose uptake, GLUT1 expression, AMPK phosphorylation, and HIF1α signaling. Mechanistically, mitochondrial remodeling was regulated in part by melatonin signaling, whereas glycolytic reprogramming was modulated by systemic circadian inputs, including feeding associated cues and Wnt/β-catenin signaling. FoxM1 and DRP1 contributed to mitochondrial quality control, while PGC1α dependent transcription supported compensatory mitochondrial biogenesis across the daily circadian cycle. These metabolic transitions were accompanied by dynamic changes in cell and nuclear size, linked to lamin A/C phosphorylation modulation. These coordinated processes defined a nocturnal state of enhanced stem cell fitness characterized by improved regenerative potential. Key features of glycolytic regulation were conserved in human HSCs, and in vitro melatonin treatment reduced the mitochondrial membrane potential and cell size of human pHSCs. Together, these findings establish a temporally regulated metabolic framework in which circadian cues partition mitochondrial and glycolytic programs to preserve stem cell maintenance and function, adding a new layer to pHSC metabolic physiology with clinical transplantation implications. - Source: PubMed
Publication date: 2026/09/21
Chakrabarti PriyasmitaSingh Abhishek KWilson Nicola KKucinski IwoKollet OritOrdonez Moreno Lizeth-AlejandraSimoni-Nieves ArturoVijayabaskar M SKinston Sarah JChang Tzu-HsuanWang Yi-HaoHaddad MontaserVaresi AngelicaPetrovich-Kopitman EkaterinaPorat ZivSmirnova TatianaPaulose JiffinChoudhuri AvikHogenesch JohnZhao You-YangHo Ping-ChihBuxboim AmnonZon Leonard IFilippi Marie-DominiqueMarkus Regina PDick John EXie Stephanie ZGottgens BertholdCancelas Jose ALapidot Tsvee - Advanced prostate cancer has increasingly developed a lethal neuroendocrine form, small cell/neuroendocrine prostate cancer (NEPC), as a consequence of the widespread use of highly potent androgen receptor signaling inhibitors in castration-resistant disease. The molecular mechanisms remain unclear and no effective therapies currently exist. We report that tryptophan hydroxylase 1 (TPH1), the enzyme responsible for peripheral serotonin biosynthesis - a neurotransmitter enriched in neuroendocrine tumors and a classical neuroendocrine biomarker - was upregulated in both de novo and therapy-induced human NEPC. TPH1 upregulation was necessary and sufficient for neuroendocrine differentiation and the NEPC phenotype through its enzymatic activity. Silencing TPH1 suppressed neuroendocrine plasticity and various aggressive behaviors of NEPC cells, including proliferation, invasion, sphere formation, and NEPC tumor xenograft growth. Mechanistically, TPH1 activated mTOR via intracellular serotonin-dependent serotonylation of mTOR at glutamine 2453, which triggered the induction of FOXM1 and E2F1 to drive NEPC differentiation and growth. Importantly, pharmacological inhibition of TPH1 using the clinically available inhibitor LX1606 effectively restricted growth and neuroendocrine marker expression in multiple NEPC cell lines and patient-derived xenografts. Collectively, these findings characterize TPH1's contribution to NEPC and suggest TPH1 as a potential therapeutic target. - Source: PubMed
Publication date: 2026/09/17
Wei JingWang JingChen JingruiZhang MichelleChen Chia-HuiPu TianjieO'Brien AliviaHargrove SephtisCorey EvaLin Tzu-PingGao Allen CWu Boyang Jason - Maternal Embryonic Leucine Zipper Kinase (MELK) is a key regulator of the G2/M checkpoint and a recognized pan-cancer oncogene; however, its regulatory mechanisms and clinical significance in lung adenocarcinoma (LUAD) remain incompletely understood. This study aimed to investigate the molecular, prognostic, immune, and therapeutic relevance of MELK in LUAD. - Source: PubMed
Publication date: 2026/08/31
Jangir KritikaKumar NiranjanSaini ChainseeVats PrernaBaweja BhavikaPatidar PrachiSoni RashiLakdawala HusenSingh Jaikee KumarNema Rajeev - FOXM1 is a cell proliferation-driving transcription factor activated by phosphorylation-induced conformational changes. In its inactive state, an intramolecular β-hairpin within the transactivation domain (TAD) binds the N-terminal repressor domain (NRD), forming a composite β-sheet that locks the protein in an autoinhibited conformation. Despite the known importance of this regulatory switch, the molecular events that unlock FOXM1 remain poorly characterized. Here, we performed 5 μs all-atom molecular dynamics simulations of human FOXM1b NRD-TAD complexes in both unphosphorylated and tetra-phosphorylated states, modeling four experimentally validated regulatory phosphosites. Our results showed that phosphorylation induces local unfolding of the β-hairpin beginning at Ser715, located at the hairpin turn, and propagates to global disruption of the NRD interface through hydrogen bond loss, salt bridge rupture, and secondary structure collapse. In contrast, the unphosphorylated complex maintains stable hairpin geometry and interdomain contacts. Additional replicate tetra-phosphorylated simulations and a monophosphorylated Ser715 simulation reproduced the β-hairpin unfolding event, supporting both reproducibility and the sufficiency of Ser715 phosphorylation in initiating this transition. Per-residue MM-PBSA energy decomposition further reveals that phosphorylation redistributes interdomain interaction energetics, with Ser715 emerging as the dominant locus of energetic perturbation despite the presence of multiple phosphosites. Together, these findings support a phosphorylation-triggered order-to-disorder transition that relieves FOXM1 autoinhibition and highlight Ser715 as a key structural and energetic switch. Our study provides a dynamic molecular framework for targeting FOXM1 activation via its regulatory fold. - Source: PubMed
AlRawashdeh SaraObidat RaghdDel Moral-Morales AylinMedina-Franco José LVelázquez-Martínez Carlos A