RT Journal Article
T1 The cerebral cavernous malformation 3 gene is necessary for senescence induction
A1 Guerrero López, Ana
A1 Iglesias García, Cristina
A1 Raguz, Selina
A1 Floridia, Ebel
A1 Gil, Jesús
A1 Pombo Ramos, Celia María
A1 Zalvide Torrente, Juan Bautista
K1 Autophagy
K1 CEBPb
K1 PDCD10
K1 SASP
AB Mutations in cerebral cavernous malformation 3 gene are knownto result in development of vascular malformations and haverecently been proposed to also give rise to meningiomas. Wereport in this study that lack of CCM3 unexpectedly impairs thesenescence response of cells, and this is related to the inability ofCCM3-deficient cells to induce the C/EBPb transcription factor andimplement the senescence-associated secretory phenotype.Induction of C/EBPb and cytokines is also impaired in the absenceof CCM3 in response to cytokines in nonsenescent cells, pointingto it being a primary defect and not secondary to impairedsenescence. CCM3-deficient cells also have a defect in autophagyat late passages of culture, and this defect is also not dependenton impaired senescence, as it is evident in immortal cells afternutrient starvation. Further, these two defects may be related, asenforcing autophagy in CCM3-deficient late passage cellsincreases C/EBPb cytokine expression. These results broaden ourknowledge on the mechanisms by which CCM3 deficiency resultsin disease and open new avenues of research into both CCM3 andsenescence biology
PB Wiley
SN 1474-9718
YR 2015
FD 2015
LK http://hdl.handle.net/10347/23069
UL http://hdl.handle.net/10347/23069
LA eng
NO Guerrero, A., Iglesias, C., Raguz, S., Floridia, E., Gil, J., Pombo, C.M. and Zalvide, J. (2015), The cerebral cavernous malformation 3 gene is necessary for senescence induction. Aging Cell, 14: 274-283. doi:10.1111/acel.12316
NO This work was supported by Xunta de Galicia grant INCITE 09 208 110 PR GCP2013‐032 (to C. M. P.), and Ministerio de Ciencia e Innovación grant SAF2011‐24940 (to J. Z.), cofinanced with Regional Development European Funds, and ERANET neuron PRI‐PIMNEU‐2011‐1337. A.G. was recipient of an FPU predoctoral fellowship from Ministerio de Ciencia e Innovación, Spain. C.I. and E.F. are recipients of a predoctoral fellowship from Xunta de Galicia, Spain
DS Minerva
RD 26 abr 2026