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Localisation sub-cellulaire des facteurs de transcription STAT5a et b et implication au cours de l'hématopoïèse maligne

Abstract : STAT (Signal Transducer and Activator of Transcription) 5a and STAT5b proteins are latent cytoplasmic transcription factors that translocate to the nucleus upon activation by cytoplasmic Jak tyrosine kinases. They participate in elemental cell biologie processes including cellular growth, cell cycle progression and apoptosis. STAT5 has been described as a common target molecule for several tyrosine kinase oncogenes associated with myeloproliferative disease, including Bcr-Abl in CML. We analyzed the sub cellular distribution of the STAT5 proteins in 70 primary AML and pointed out a nucleolar STAT5 localization associated with AML5 and CML phenotypes. The STAT5 nucleolar localization was corroborated in the K562 cell line. We demonstrated a nucleolar localization restricted to STAT5[beta] proteins. Neither Bcr-Abl activation nor proteasome-mediated protein degradation can explain the STAT5 nucleolar localization in CML as STI561/MG132-inhibition treatments do not contribute to STAT nucleolar delocalization. This is, to our knowledge, the first evidence of a nucleolar translocation of STAT transcription factors in hematological malignancies. Moreover, because the STAT5 nucleolar distribution is restricted to AML5 and CML it could be hypothesized that it might be part of these leukaemic phenotypes.
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Theses
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http://docnum.univ-lorraine.fr/prive/SCD_T_2004_0253_TOUCHE.pdf
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https://hal.univ-lorraine.fr/tel-01746958
Contributor : Thèses Ul <>
Submitted on : Thursday, March 29, 2018 - 10:48:35 AM
Last modification on : Tuesday, September 1, 2020 - 2:11:41 PM

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Nadège Touche. Localisation sub-cellulaire des facteurs de transcription STAT5a et b et implication au cours de l'hématopoïèse maligne. Biologie moléculaire. Université Henri Poincaré - Nancy 1, 2004. Français. ⟨NNT : 2004NAN10253⟩. ⟨tel-01746958⟩

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