ECD

Last update 08 May 2025

Basic Info

Synonyms

ECD, ecdysoneless cell cycle regulator, GCR2

+ [3]

Introduction

Regulator of p53/TP53 stability and function. Inhibits MDM2-mediated degradation of p53/TP53 possibly by cooperating in part with TXNIP (PubMed:16849563, PubMed:23880345). May be involved transcriptional regulation. In vitro has intrinsic transactivation activity enhanced by EP300. May be a transcriptional activator required for the expression of glycolytic genes (PubMed:19919181, PubMed:9928932). Involved in regulation of cell cycle progression. Proposed to disrupt Rb-E2F binding leading to transcriptional activation of E2F proteins (PubMed:19640839). The cell cycle -regulating function may depend on its RUVBL1-mediated association with the R2TP complex (PubMed:26711270). May play a role in regulation of pre-mRNA splicing (PubMed:24722212). Participates together with DDX39A in mRNA nuclear export (PubMed:33941617).

100 Clinical Results associated with ECD

100 Translational Medicine associated with ECD

0 Patents (Medical) associated with ECD

594

Literatures (Medical) associated with ECD

15 Apr 2025·Journal of Clinical Investigation

Identification of potent biparatopic antibodies targeting FGFR2 fusion–driven cholangiocarcinoma

Article

Author: Sinopoli, Alessandro ; Chang, Liang ; Rodriguez, Diego J ; Chaturantabut, Saireudee ; Chang, Yuan-Chen ; Dzvurumi, Ruvimbo ; Atari, Adel ; Frederick, Dennie T ; He, Yao ; Tseng, Yuen-Yi ; Kesar, Devishi ; Kim, Jiwan J ; Bardeesy, Nabeel ; Oliver, Sydney ; Robinson, Foxy P ; Song, Tian-Yu ; Sellers, William R ; Ching, Meilani

Translocations involving FGFR2 gene fusions are common in cholangiocarcinoma and predict response to FGFR kinase inhibitors. However, response rates and durability are limited due to the emergence of resistance, typically involving FGFR2 kinase domain mutations, and to suboptimal dosing, relating to drug adverse effects. Here, we develop biparatopic antibodies targeting the FGFR2 extracellular domain (ECD) as candidate therapeutics. Biparatopic antibodies can overcome drawbacks of bivalent monospecific antibodies, which often show poor inhibitory or even agonist activity against oncogenic receptors. We show that oncogenic transformation by FGFR2 fusions requires an intact ECD. Moreover, by systematically generating biparatopic antibodies targeting distinct epitope pairs in FGFR2 ECD, we identified antibodies that effectively block signaling and malignant growth driven by FGFR2 fusions. Importantly, these antibodies demonstrate efficacy in vivo, synergy with FGFR inhibitors, and activity against FGFR2 fusions harboring kinase domain mutations. Thus, we believe that biparatopic antibodies may serve as an innovative treatment option for patients with FGFR2-altered cholangiocarcinoma.

01 Feb 2025·Journal of Biotechnology

Improved biosynthesis of tyrosol by epigenetic modification-based regulation and metabolic engineering in Saccharomyces cerevisiae

Article

Author: Wu, Zhenke ; Li, Defang ; Fan, Bengui ; Wang, Jun ; Liang, Xiqin ; An, Tianyue ; Wang, Guoli ; Zheng, Qiusheng

Aromatic amino acids and their derivatives are high value chemicals widely used in food, pharmaceutical and feed industries. Current preparation methods for aromatic amino acid products are fraught with limitations. In this study, the efficient biosynthesis of aromatic amino acid compound tyrosol was investigated by epigenetic modification-based regulation and optimization of the biosynthetic pathway of aromatic amino acids. The production of tyrosol was significantly improved by the overexpression of m⁶A modification writer Ime4 and reader Pho92, and the positive regulator Gcr2. Introduction of Bbxfpk and deletion of Gpp1 further improved tyrosol production. Then the feedback inhibition of the shikimate pathway was relieved by the mutants Aro4^K229L and Aro7^G141S. The final tyrosol producing engineered strain was constructed by the deletion of PHA2, replacement of the native promoter of ARO10 with the strong promoter PGK1p, and introduction of tyrosine decarboxylase PcAAS. In the background of m⁶A modification regulation, this strain ultimately produced 954.69 ± 43.72 mg/L of tyrosol, promoted by 61.7-fold in shake-flask fermentation.

01 Feb 2025·Leukemia

A CADASIL NOTCH3 mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878H hematopoietic clones

Article

Author: Hardas, Alexandros ; Kalampalika, Foteini ; Sánchez-Lanzas, Raúl ; Ganuza, Miguel ; Barclay, Justin ; Gallipoli, Paolo ; Jiménez-Pompa, Amanda

AbstractClonal hematopoiesis (CH) is nearly universal in the elderly. The molecular and cellular mechanisms driving CH and the clinical consequences of carrying clonally derived mutant mature blood cells are poorly understood. We recently identified a C223Y mutation in the extracellular domain (ECD) of NOTCH3 as a putative CH driver in mice. Provocatively, germline NOTCH3 ECD mutations perturbing cysteine numbers cause Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), a type of vascular dementia, suggesting an unexpected link between CADASIL and CH. Here, we formally demonstrated that mouse hematopoietic stem and progenitor cells (HSPCs) expressing CADASIL-related NOTCH3C455R exhibit a proliferative advantage resulting in robust cellular expansion in vivo and in vitro. Co-expression of NOTCH3C455R and Dnmt3aR878H, homologous to a frequent human CH mutation, increased the fitness of NOTCH3C455R HSPCs, demonstrating their functional cooperation. Surprisingly, the presence of NOTCH3C455R hematopoietic cells supported the expansion of Dnmt3aR878H HSPCs in a non-cell autonomous fashion in vivo, strongly suggesting that CADASIL patients and asymptomatic carriers can be highly predisposed to DNMT3AR882H-driven CH. Considering that CADASIL-related NOTCH3 mutations are more frequent in the general population than anticipated (~1 carrier in 400 people), the effect of these NOTCH3 mutations on CH development should be considered.

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