The cerebral cavernous malformation 3 gene is necessary for senescence induction
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Identificadores
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Fecha de publicación
2015Título de revista
AGING CELL
Tipo de contenido
Artigo
DeCS
Mutación | Proteínas Proto-Oncogénicas | Proteínas Reguladoras de la Apoptosis | Proteínas de la Membrana | Senescencia CelularMeSH
Apoptosis Regulatory Proteins | Cellular Senescence | Cellular Senescence | Membrane Proteins | Mutation | Proto-Oncogene ProteinsResumen
Mutations in cerebral cavernous malformation 3 gene are known to result in development of vascular malformations and have recently been proposed to also give rise to meningiomas. We report in this study that lack of CCM3 unexpectedly impairs the senescence response of cells, and this is related to the inability of CCM3-deficient cells to induce the C/EBPβ transcription factor and implement the senescence-associated secretory phenotype. Induction of C/EBPβ and cytokines is also impaired in the absence of CCM3 in response to cytokines in nonsenescent cells, pointing to it being a primary defect and not secondary to impaired senescence. CCM3-deficient cells also have a defect in autophagy at late passages of culture, and this defect is also not dependent on impaired senescence, as it is evident in immortal cells after nutrient starvation. Further, these two defects may be related, as enforcing autophagy in CCM3-deficient late passage cells increases C/EBPβ cytokine expression. These results broaden our knowledge on the mechanisms by which CCM3 deficiency results in disease and open new avenues of research into both CCM3 and senescence biology.
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