Apoptosis Signating Pathways and Biological Effects of TGFB
název v českém jazyce není uveden
dissertation thesis (DEFENDED)

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Permanent link
http://hdl.handle.net/20.500.11956/6453Collections
- Kvalifikační práce [3505]
Author
Advisor
Referee
Brdička, Radim
Holada, Karel
Faculty / Institute
First Faculty of Medicine
Discipline
-
Department (external)
Information is unavailable
Date of defense
14. 6. 2006
Publisher
Univerzita Karlova, 1. lékařská fakultaLanguage
English
Grade
Pass
Keywords
Keywords not foundApoptosis is necessary for maintaing the integrity of all alive multicellular organisms and therefore needs to be precisely regulated. Very important regulators of apoptosis are pleiotropic cytokines from TFGβ superfamily (e.g. TGFβ, BMP, aktivins), whose signals are transduced by SMAD proteins. Patients with secondary myelodysplasias and acute myeloid leukemias (MDS/AML) frequently exhibit interstitial deletions of the chromosome-5q resulting in hemizygous loss of the transcription transactivator SMAD5. SMAD5 is a member of the signal transducer family conveying the pleiotropic TGFβ/BMP cytokine signals with roles in development, cell growth control, and tumor progression. Consistent Smad5 gene expression in these cell types and the gradual increase in its mRNA and protein levels in a model of induced erythroid differentiation of murine erythroleukemia (MEL) cells suggest a role of the gene in hematopoiesis. We show that bone morphogenetic protein 4 (BMP4) directs Smad5 activation in human hematopoietic cells, as monitored at the levels of protein phosphorylation, nuclear translocation, and specific transcription response. In vitro induction of normal human CD34+ cells by BMP4 results in significantly increased proliferation of erythroid progenitors (BFU-E) and formation of glycophorin- A+ cells, whereas...