Search results for "PARP"

The nucleosome-remodeling ATPase ISWI is regulated by poly-ADP-ribosylation.

2008

ATP-dependent nucleosome-remodeling enzymes and covalent modifiers of chromatin set the functional state of chromatin. However, how these enzymatic activities are coordinated in the nucleus is largely unknown. We found that the evolutionary conserved nucleosome-remodeling ATPase ISWI and the poly-ADP-ribose polymerase PARP genetically interact. We present evidence showing that ISWI is target of poly-ADP-ribosylation. Poly-ADP-ribosylation counteracts ISWI function in vitro and in vivo. Our work suggests that ISWI is a physiological target of PARP and that poly-ADP-ribosylation can be a new, important post-translational modification regulating the activity of ATP-dependent nucleosome remodel…

Differentiative pathway activated by 3-aminobenzamide in human osteosarcoma MG-63 cells involves FAK and PAK activities.

2006

Targeting components of the alternative NHEJ pathway sensitizes KRAS mutant leukemic cells to chemotherapy.

2014

Abstract Activating KRAS mutations are detected in a substantial number of hematologic malignancies. In a murine T-cell acute lymphoblastic leukemia (T-ALL) model, we previously showed that expression of oncogenic Kras induced a premalignant state accompanied with an arrest in T-cell differentiation and acquisition of somatic Notch1 mutations. These findings prompted us to investigate whether the expression of oncogenic KRAS directly affects DNA damage repair. Applying divergent, but complementary, genetic approaches, we demonstrate that the expression of KRAS mutants is associated with increased expression of DNA ligase 3α, poly(ADP-ribose) polymerase 1 (PARP1), and X-ray repair cross-comp…

The effect of 3-aminobenzamide, inhibitor of poly(ADP-ribose) polymerase, on human osteosarcoma cells

2003

This study demonstrates that in human osteosarcoma cells treatment with 3-aminobenzamide (3-AB), a potent inhibitor of poly(ADP-ribose) polymerase (PARP), induces morphological and biochemical features of differentiation, the duration of which depends on whether or not the normal RB gene is expressed. In Saos-2 cells expressing a non-functional Rb protein, 3-AB treatment induced the formation of transient, short dendritic-like protrusions. In RB-transfected-Saos-2 cells (a clone previously generated in our laboratory that shows stable expression of wild-type Rb protein), 3-AB induced marked and prolonged changes with the formation of long dendritic-like protrusions and the appearance of ste…

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

2019

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…

Regulation of Chromatin Remodeling through poly-ADP-ribosylation

2008

Differentiative pathway activated by 3-aminobenzamide, an inhibitor of PARP, in human osteosarcoma MG-63 cells

2004

AbstractThis study describes the molecular mechanism by which treatment with 3-AB, a potent inhibitor of PARP, allows human osteosarcoma MG-63 cells to restrict growth and enter differentiation. Our findings show that in MG-63 cells, aberrant gene expression keeps Rb protein constitutively inactivated through hyperphosphorylation and this promotes uncontrolled proliferation of the cells. After 3-AB-treatment, the poly(ADP-ribosyl)ation of nuclear proteins markedly decreases and this results in an increase in both the hypophosphorylated active form of Rb and pRb/E2F complexes. These effects are accompanied by G1 arrest, downregulation of gene products required for proliferation (cyclin D1, β…

The Nucleosome Remodeling ATPase ISWI is Regulated by poly-ADP-ribosylation

2008

Arte mueble de la España mediterránea : Breve síntesis y algunas consideraciones teóricas

1994

En este trabajo se analiza el arte mueble de/Mediterráneo español, basándose especialmente en la colección de plaquetas de El Parpalló. El estudio detallado de los motivos artísticos y su correlación estratigráfica revela algunas diferencias cronológicas en un marco de evolución continua. Conceptos tradicionales, como el de “Provincia Mediterránea‘~ son revisados a la luz de nuevos enfoques teóricosy empíricos. Portable art of Mediterranean Spain is analyzed in this paper with special reference (o the more than five thousand decoratedplaquettesfrom El Parpalló. A detailed study of artistic mot¡fs and stratigraphy reveals some chronological differences inside a frame of continous evolution. …

La Sala Parpalló en el Centre Cultural La Beneficència (1995-1999)

2020

During the period 1995-1999, the Sala Parpalló was located in the Beneficència Cultural Center of Valencia, sharing the place with the spaces of the Museum of Prehistory, the Museum of Ethnology and the IVEI. In the investigation it exposed a technical file for each of the 57 self-produced exhibitions carried out in the period and a selection of the studies that accompanied them: the files are displayed chronologically according to the procedures used. The work concludes with the analysis of the objectives that were mainly all the programming: 1) Sala Parpalló as an integrated project; 2) Studies and exhibitions around the Valencian Cultural Imaginary; 3) Analysis of the postmodern crisis; …