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Promyelocytic Leukaemia Protein and Deffect of Transforming Growth Factor-beta Signalling in Acute Promyelocytic Leukaemia


Authors: O. Fuchs;  D. Provazníková;  G. Pešlová
Authors‘ workplace: Ústav hematologie a krevní transfuze, Praha
Published in: Čas. Lék. čes. 2005; 144: 90-94
Category: Review Article

Overview

Chromosome translocations are detected in 50-70 % of human leukaemia. The promyelocytic leukaemia (PML) gene is involved in the t(15;17) chromosomal translocation of acute promyelocytic leukaemia (APL). PML gene encodes a protein, which was shown to be concentrated in PML-nuclear bodies. Histone acetyltransferases and deacetylases, and chromatin-modifying proteins are accumulated in complexes with PML protein in these nuclear bodies giving the evidence of their role in transcription regulation. Physical interactions of PML protein with transcription factors, co-activators and co-repressors of transcription correspond with the role of PML in transcription regulation. PML plays an important role in apoptosis, proliferation and senescence of cells. PML gene is a tumour-suppressor gene and a product of its expression acts as a potent cell growth suppressor. All these activities of PML protein are ascribed to its nuclear functions. Cytoplasmic form of PML (cPML) is also very important and it is critical for transforming growth factor-β (TGF-β) signalling. Cytoplasmic PML interacts with two TGF-β receptors (TβRI and TβRII) and acts as a bridging factor between protein called Smad anchor of receptor activation (SARA) and Smad proteins and it plays a role in the transport of whole complex into the early endosomes in TGF-β signalling. The loss of functional cPML induces not only APL but it might influence behaviour of cancer cells and their resistance to TGF-β. 

Key words:
acute promyelocytic leukaemia, promyelocytic leukaemia protein, SARA protein, Smad proteins, transforming growth factor-beta.


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Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental Hygienist

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Journal of Czech Physicians


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