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ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells

Wang, Y ; Godin-Heymann, N ; Dan Wang, X ; Bergamaschi, D ; Llanos, S ; Lu, X

Cell death and differentiation, 2013-04, Vol.20 (4), p.525-534 [Periódico revisado por pares]

England: Nature Publishing Group

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ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells
Autor: Wang, Y ; Godin-Heymann, N ; Dan Wang, X ; Bergamaschi, D ; Llanos, S ; Lu, X
Assuntos: Adaptor Proteins, Signal Transducing - antagonists & inhibitors ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Amino acids ; Animals ; Apoptosis ; Apoptosis Regulatory Proteins - antagonists & inhibitors ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Autophagy ; Cancer ; Cancer research ; Cell cycle ; Cell death ; Cell growth ; Cell Line ; Clinical medicine ; Epidermal growth factor ; Humans ; Kinases ; Localization ; MCF-7 Cells ; Medical research ; Mice ; Mutation ; Oncogenes ; Original Paper ; p53 protein ; Protein Binding ; Proteins ; ras Proteins - antagonists & inhibitors ; ras Proteins - genetics ; ras Proteins - metabolism ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - genetics ; RNA Interference ; RNA, Small Interfering - metabolism ; Senescence ; Signal Transduction ; Transcription ; Tumor Suppressor Protein p53 - metabolism ; Tumors
É parte de: Cell death and differentiation, 2013-04, Vol.20 (4), p.525-534
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These authors contributed equally to this work.
Present address: Centre for Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK.
Present address: Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Present address: Geriatric Nephrology Department, South Building, Chinese PLA General Hospital, Beijing 100853, China.
Descrição: RAS mutations occur frequently in human cancer and activated RAS signalling contributes to tumour development and progression. Apart from its oncogenic effects on cell growth, active RAS has tumour-suppressive functions via its ability to induce cellular senescence and apoptosis. RAS is known to induce p53-dependent cell cycle arrest, yet its effect on p53-dependent apoptosis remains unclear. We report here that apoptosis-stimulating protein of p53 (ASPP) 1 and 2, two activators of p53, preferentially bind active RAS via their N-terminal RAS-association domains (RAD). Additionally, ASPP2 colocalises with and contributes to RAS cellular membrane localisation and potentiates RAS signalling. In cancer cells, ASPP1 and ASPP2 cooperate with oncogenic RAS to enhance the transcription and apoptotic function of p53. Thus, loss of ASPP1 and ASPP2 in human cancer cells may contribute to the full transforming property of RAS oncogene.
Editor: England: Nature Publishing Group
Idioma: Inglês

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ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells

Wang, Y ; Godin-Heymann, N ; Dan Wang, X ; Bergamaschi, D ; Llanos, S ; Lu, X

England: Nature Publishing Group

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