title: Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence.
abstract: Cellular senescence acts as a potent barrier for tumour initiation and progression. Previous studies showed that the PML tumour suppressor promotes senescence, although the precise mechanisms remain to be elucidated. Combining gene expression profiling with chromatin-binding analyses and promoter reporter studies, we identify TBX2, a T-box transcription factor frequently overexpressed in cancer, as a novel and direct PML-repressible E2F-target gene in senescence but not quiescence. Recruitment of PML to the TBX2 promoter is dependent on a functional p130/E2F4 repressor complex ultimately implementing a transcriptionally inactive chromatin environment at the TBX2 promoter. TBX2 repression actively contributes to senescence induction as cells depleted for TBX2 trigger PML pro-senescence function(s) and enter senescence. Reciprocally, elevated TBX2 levels antagonize PML pro-senescence function through direct protein-protein interaction. Collectively, our findings indicate that PML and TBX2 act in an autoregulatory loop to control the effective execution of the senescence program.
authors: Department of Cell Biology and Infection, Nuclear Organisation and Oncogenesis Laboratory, Institut Pasteur, Paris, France.
authors: Nadine
authors: N
authors: Martin
authors: Moussa
authors: M
authors: Benhamed
authors: Karim
authors: K
authors: Nacerddine
authors: Maud D
authors: MD
authors: Demarque
authors: Maarten
authors: M
authors: van Lohuizen
authors: Anne
authors: A
authors: Dejean
authors: Oliver
authors: O
authors: Bischof
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000071156:Promyelocytic Leukemia Protein; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins