[Promyelocytic leukaemia protein and defect in transforming growth factor-beta signal pathway in acute promyelocytic leukaemia].
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-beta (TGF-beta) signalling. Cytoplasmic PML interacts with two TGF-beta receptors (TbetaBRI and TbetaRII) 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-beta signalling. The loss of functional cPML induces not only APL but it might influence behaviour of cancer cells and their resistance to TGF-beta.
Fuchs
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O
Ustav hematologie a krevní transfuze, Praha. ota.fuchs@uhkt.cz
Provazníková
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Peslová
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D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000071156:Promyelocytic Leukemia Protein; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; C116420:ZFYVE16 protein, human; D012697:Serine Endopeptidases