Enriching the Arsenal of Pharmacological Tools against MICAL2

Barravecchia, Ivana; Barresi, Elisabetta; Russo, Camilla; Scebba, Francesca; Cesari, Chiara De; Mignucci, Valerio; Luca, Davide De; Salerno, Silvia; Pietra, Valeria La; Giustiniano, Mariateresa; Pelliccia, Sveva; Brancaccio, Diego; Donati, Greta; Settimo, Federico Da; Taliani, Sabrina; Angeloni, Debora; Marinelli, Luciana

doi:10.3390/molecules26247519

Cited by 4 publications

(2 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They could mediate Semaphorin3A-NRP2 response to VEGFR1 in rat ECs and enter the p130Cas interactome in reaction to VEGF in HUVEC 33 . Previous evidence had shown MICAL2 was strongly expressed in metastasizing cancer cells, especially at the invasive front and in the neo-angiogenic vasculature 34 . MICAL2 was also involved in angiogenesis and vascular development pathways based on whole-genome gene expression pro ling 33 .…”

Section: Discussionmentioning

confidence: 94%

Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Lung Squamous Cell Carcinoma

Cao

Yang

Jiang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Cancer-associated fibroblasts (CAFs) are vital in tumorigenesis, metastasis, and response to therapy. This study aimed to explore the characteristics of CAFs in lung squamous cell carcinoma (LUSC) and to develop a CAF-based risk signature for predicting the prognosis of this disease. Methods: The mRNA expression and clinical information of 235 LUSC samples were obtained from the Gene Expression Omnibus (GEO) database (GSE 157010). 498 LUSC samples were obtained from the Cancer Genome Atlas (TCGA)-LUSC database. We identified stromal CAF-related genes using weighted gene co-expression network analysis (WGCNA). The CAF risk signature was built through cox regression. We utilized the Spearman test to clarify the correlation among CAF risk score, CAF markers, and CAF infiltrations. The gene set enrichment analysis (GSEA) was then applied to explore the molecular mechanisms underlying. Result: The 3-gene (EFEMP2, MICAL2, and CRISPLD2) prognostic CAF model was constructed. LUSC patients were divided into high- and low-CAF-risk groups based on their median CAF risk score. Those with high CAF risk scores showed significantly worse prognoses. The CAF risk score was highly positively related to stromal and CAF infiltrations. Besides, the 3-gene model presented substantial accordance with CAF markers. ECM receptor interaction, MAPK, and TGF-β signaling pathway were reported as pivotal roles in the CAF risk model by GSEA. Conclusion:The 3-gene prognostic CAF signature could predict prognosis efficiently for LUSC patients. Our findings will provide new knowledge for potential guiding tailored antiCAF therapy for LUSC patients.

show abstract

Section: Discussionmentioning

confidence: 94%

Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Lung Squamous Cell Carcinoma

Cao

Yang

Jiang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…MICAL1 is required for synapse development 14,15 , while both MICAL1 and MICAL3 contribute to cytokinesis and vesicle trafficking by regulating F-actin disassembly [16][17][18][19] . Additionally, MICAL2 has been implicated in cancer cell functions and is considered as a potential drug target 20,21 .…”

Section: Mainmentioning

confidence: 99%

Autoinhibition and Activation Mechanisms for MICAL Monooxygenases in F-actin Disassembly

Wei,

Lin,

Dong

et al. 2024

Preprint

View full text Add to dashboard Cite

MICAL (Molecule Interacting with CasL) proteins represent a unique family of actin regulators crucial for synapse development, membrane trafficking, and cytokinesis. Unlike classical actin regulators, MICAL proteins possess enzymatic activity, catalyzing the oxidation of specific residues within actin filaments to induce robust filament severing. The potent activity of MICAL proteins requires tight control to prevent extensive damage to the actin cytoskeleton. Due to limited structural information on full-length MICAL proteins, the molecular mechanisms governing MICAL autoinhibition and activation remain elusive. Here, we reported the cryo-EM structure of full-length MICAL1, unveiling a head-to-tail interaction that allosterically blocks enzymatic activity through the binding of the C-terminal Rab-binding domain (RBD) to the N-terminal monooxygenase domain. The structure also reveals the assembly of C-terminal domains via a tripartite interdomain interaction, stabilizing the inhibitory conformation of the RBD. Our structural, biochemical, and cellular analyses elucidate the transition from the autoinhibited to activated conformation of MICAL1 in response to Rab8-subfamily GTPase. Dual Rab-binding to the RBD induces the conformation rearrangement of the RBD and synergistically promotes the autoinhibition-to-activation transition, revealing intricate activity regulation mechanisms for MICAL proteins. Furthermore, our mutagenesis study of MICAL3 suggests a conserved autoinhibition and activation mechanism among MICAL proteins.

show abstract

Autoinhibition and relief mechanisms for MICAL monooxygenases in F-actin disassembly

Lin,

Dong,

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Enriching the Arsenal of Pharmacological Tools against MICAL2

Cited by 4 publications

References 22 publications

Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Lung Squamous Cell Carcinoma

Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Lung Squamous Cell Carcinoma

Autoinhibition and Activation Mechanisms for MICAL Monooxygenases in F-actin Disassembly

Autoinhibition and relief mechanisms for MICAL monooxygenases in F-actin disassembly

Contact Info

Product

Resources

About