RT Journal Article
T1 PARP1 Deficiency Reduces Tumour Growth by Decreasing E2F1 Hyperactivation: A Novel Mechanism in the Treatment of Cancer
A1 Iglesias, Pablo
A1 Seoane Souto, Marcos
A1 Golán Cancela, Irene
A1 Castro Piedras, Isabel
A1 Fraga Rodríguez, Máximo
A1 Arce Vázquez, Víctor Manuel
A1 Costoya Puente, José Antonio
K1 Poly (ADP-Ribose) Polymerase-1
K1 E2F1 transcription factor
K1 Cell cycle
K1 Neoplasm
K1 Glioma
K1 Animal disease models
AB In recent years, poly (ADP-ribose) polymerase (PARP) inhibitors have been evaluated for treating homologous recombination-deficient tumours, taking advantage of synthetic lethality. However, increasing evidence indicates that PARP1 exert several cellular functions unrelated with their role on DNA repair, including function as a co-activator of transcription through protein-protein interaction with E2F1. Since the RB/E2F1 pathway is among the most frequently mutated in many tumour types, we investigated whether the absence of PARP activity could counteract the consequences of E2F1 hyperactivation. Our results demonstrate that genetic ablation of Parp1 extends the survival of Rb-null embryos, while genetic inactivation of Parp1 results in reduced development of pRb-dependent tumours. Our results demonstrate that PARP1 plays a key role as a transcriptional co-activator of the transcription factor E2F1, an important component of the cell cycle regulation. Considering that most oncogenic processes are associated with cell cycle deregulation, the disruption of this PARP1-E2F1 interaction could provide a new therapeutic target of great interest and a wide spectrum of indications
PB MDPI
YR 2020
FD 2020
LK http://hdl.handle.net/10347/23767
UL http://hdl.handle.net/10347/23767
LA eng
NO Iglesias, P.; Seoane, M.; Golán, I.; Castro-Piedras, I.; Fraga, M.; Arce, V.M.; Costoya, J.A. PARP1 Deficiency Reduces Tumour Growth by Decreasing E2F1 Hyperactivation: A Novel Mechanism in the Treatment of Cancer. Cancers 2020, 12, 2907
NO This work received financial support from the Ministerio de Ciencia e Innovación (SAF2008-00543 and SAF2009-08629; J.A.C.) and ISCIII, Ministerio de Economía y Competitividad (PI15/01129), the Consellería de Cultura, Educación e Ordenación Universitaria (GPC2014/030, INCITE08PXIB208091PR and PXIB208091PR; J.A.C.), PRE/2011/131 (I.G.C.), the Centro Singular de Investigación de Galicia accreditation 2016–2019, ED431G/05), and the European Regional Development Fund (ERDF)
DS Minerva
RD 27 abr 2026