Research publications

Found 2 publicacions matching the indicated search criteria.
Fernández-Simón E, Suárez-Calvet X, Carrasco-Rozas A, Piñol-Jurado P, López-Fernández S, Pons G, Bech Serra JJ, de la Torre C, de Luna N, Gallardo E, Díaz-Manera J

RhoA/ROCK2 signalling is enhanced by PDGF-AA in fibro-adipogenic progenitor cells: implications for Duchenne muscular dystrophy.

Journal of Cachexia Sarcopenia and Muscle 4 Apr 2022, (13) 1373–1384. Epub 7 Feb 2022
The lack of dystrophin expression in Duchenne muscular dystrophy (DMD) induces muscle fibre and replacement by fibro-adipose tissue. Although the role of some growth factors in the process of fibrogenesis has been studied, pathways activated by PDGF-AA have not been described so far. Our aim was to study the molecular role of PDGF-AA in the fibrotic process of DMD.
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Jeannine Diesch, Marguerite-Marie Le Pannérer, René Winkler, Raquel Casquero, Matthias Muhar, Mark van der Garde, Michael Maher, Carolina Martínez Herráez, Joan J. Bech-Serra, Michaela Fellner, Philipp Rathert, Nigel Brooks, Lurdes Zamora, Antonio Gentilella, Carolina de la Torre, Johannes Zuber, Katharina S. Götze & Marcus Buschbeck

Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis

Nat Commun 12, 6060 (2021). 18 Oct 2021, .
The nucleotide analogue azacitidine (AZA) is currently the best treatment option for patients with high-risk myelodysplastic syndromes (MDS). However, only half of treated patients respond and of these almost all eventually relapse. New treatment options are urgently needed to improve the clinical management of these patients. Here, we perform a loss-of-function shRNA screen and identify the histone acetyl transferase and transcriptional co-activator, CREB binding protein (CBP), as a major regulator of AZA sensitivity. Compounds inhibiting the activity of CBP and the closely related p300 synergistically reduce viability of MDS-derived AML cell lines when combined with AZA. Importantly, this effect is specific for the RNA-dependent functions of AZA and not observed with the related compound decitabine that is only incorporated into DNA. The identification of immediate target genes leads us to the unexpected finding that the effect of CBP/p300 inhibition is mediated by globally down regulating protein synthesis.