Etude du mécanisme de répression transcriptionnelle exercé par le suppresseur de tumeur PLZF (promyelocytic leukemia zinc finger)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

HDAC4 mediates transcriptional repression by the acute promyelocytic leukaemia-associated protein PLZF

International audiencePLZF, the promyelocytic leukaemia zinc-finger protein, is a transcriptional repressor essential to development. In some acute leukaemias, a chromosomal translocation fusing the PLZF gene to that encoding the retinoic acid receptor RARalpha gives rise to a fusion protein, PLZF-RARalpha, thought to be responsible for constitutive repression of differentiation-associated genes in these cells. Repression by both PLZF and PLZF-RARalpha is sensitive to the histone deacetylase inhibitor TSA, and PLZF was previously shown to interact physically with HDAC1, a class I histone deacetylase. We here asked whether class II histone deacetylases, known to be generally involved in differentiation processes, participate in the repression mediated by PLZF and PLZF-RARalpha, and found that PLZF interacts with HDAC4 in both GST-pull-down and co-immunoprecipitation assays. Furthermore, HDAC4 is indeed involved in PLZF and PLZF-RARalpha-mediated repression, since an enzymatically dead mutant of HDAC4 released the repression, as did an siRNA that blocks HDAC4 expression. Taken together, our data indicate that recruitment of HDAC4 is necessary for PLZF-mediated repression in both normal and leukaemic cells

Impact des facteurs nutritionnels pendant et après cancer

International audienceNutritional factors (diet, weight, alcohol, physical activity) are identified as factors having an impact on the onset of several cancer sites. Less abundant scientific data also underline their impact on the tumor progression. A review of the scientific literature was carried out by a group of experts established by the French National Cancer Institute (INCa) to better document the influence of nutritional factors during and after cancer on outcomes such as overall mortality, cancer specific mortality, recurrence, second primary cancers and quality of life. This analysis of the literature completes messages of reduction of alcohol consumption, prevention of undernutrition or excess weight and adherence to dietary recommendations, avoiding the use of dietary supplements, fasting or restrictive diets and strengthens messages promoting the practice of physical activity and the fight against sedentary lifestyle.Les facteurs nutritionnels (alimentation, poids, alcool, activité physique) sont identifiés comme des facteurs ayant un impact sur l’apparition de cancers pour plusieurs localisations. Des données scientifiques, quoique moins abondantes, soulignent leur impact également sur l’évolution de la maladie. Un état des lieux des connaissances a été réalisé, par un groupe d’experts, réunis par l’Institut national du cancer (INCa), pour mieux documenter l’influence des facteurs nutritionnels pendant et après la maladie cancéreuse sur des paramètres tels que la mortalité globale, la mortalité spécifique, le risque de récidive et de second cancer primitif et la qualité de vie. Cette analyse de la littérature permet de compléter les messages de réduction de la consommation d’alcool, de prévention de la dénutrition ou de l’excès de poids et du respect des recommandations de consommation alimentaire, sans recourir aux compléments alimentaires, ni au jeûne ou régimes restrictifs et de renforcer les messages de promotion de la pratique d’activité physique et de lutte contre la sédentarité