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Thrombopoietin upregulates nucleolin mRNA and protein in thrombopoietin-dependent megakaryocytic cell line, UT-7/TPO.
- Source :
-
Molecular and cellular biochemistry [Mol Cell Biochem] 2003 May; Vol. 247 (1-2), pp. 75-82. - Publication Year :
- 2003
-
Abstract
- Thrombopoietin (TPO) is a hematopoietic cytokine that regulates megakaryocytosis and thrombocytosis by binding to its receptor (c-Mpl). The signaling pathways downstream of c-Mpl include the Ras/Raf/MAP kinase and JAK/STAT pathway and are transduced into the regulation of immediate early-, early- and delayed-response genes. How these genes couple c-Mpl activation to the biochemical machinery of cell growth and cell cycle progression in hematopoietic cells is still unclear. UT-7/TPO is a recently characterized TPO-dependent cell line. Using RNA fingerprinting with arbitrarily primed PCR (RAP-PCR) to identify the TPO-regulated genes in this cell line, we found that the mRNA expression of nucleolin was upregulated in the UT-7/TPO cells in response to TPO. Concomitantly, the TPO-stimulated cells expressed an increased amount of full length nucleolin as determined by immunoblot analysis. The TPO-induced upregulation of nucleolin mRNA was not inhibited by the MEK1/2 inhibitor PD98059, suggesting that ERK/MAPK activation is not necessary for elevation of nucleolin gene expression in response to TPO in UT-7/TPO. Nucleolin is a multifunctional nucleolar protein thought to be involved in many cellular processes, including ribosome biogenesis, the processing of ribosomal RNA (rRNA), mRNA stability, transcriptional regulation, and cell proliferation. Thus, these results indicate that the upregulation of nucleolin mRNA and protein may be important for the TPO-induced effects of hematopoietic cells.
- Subjects :
- Base Sequence
Cell Line
Cells, Cultured
Enzyme Inhibitors pharmacology
Flavonoids pharmacology
Gene Expression Profiling methods
Megakaryocytes drug effects
Mitogen-Activated Protein Kinases antagonists & inhibitors
Mitogen-Activated Protein Kinases metabolism
Molecular Sequence Data
Phosphoproteins drug effects
Polymerase Chain Reaction methods
RNA, Messenger drug effects
RNA-Binding Proteins drug effects
Sequence Analysis, DNA
Sequence Homology, Nucleic Acid
Nucleolin
Megakaryocytes cytology
Phosphoproteins genetics
Phosphoproteins metabolism
RNA-Binding Proteins genetics
RNA-Binding Proteins metabolism
Thrombopoietin pharmacology
Up-Regulation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0300-8177
- Volume :
- 247
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12841634
- Full Text :
- https://doi.org/10.1023/a:1024184116764