Differential regulation of SOCS genes in normal and transformed erythroid cells
| Autor: | Robyn Starr, Mohinder Sarna, Samantha J Busfield, Winald Lepere, S. Peter Klinken, Melissa S. Sayer, Warren S. Alexander, Thomas Bittorf, Evan Ingley, Michael J Wright, Vanessa S. Cull, Douglas J. Hilton, David J. McCarthy, David Chappell, Peta A. Tilbrook, Stephanie S. Watowich, Gene A. Palmer |
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| Rok vydání: | 2003 |
| Předmět: |
Transcriptional Activation
inorganic chemicals Cancer Research Cellular differentiation Suppressor of Cytokine Signaling Proteins Biology behavioral disciplines and activities Article Immediate-Early Proteins Mice Suppressor of Cytokine Signaling 1 Protein LYN Receptors Erythropoietin otorhinolaryngologic diseases Genetics Animals RNA Messenger Promoter Regions Genetic Erythropoietin Molecular Biology Cells Cultured Erythroid Precursor Cells Cell Line Transformed Regulation of gene expression Proteins Cell Differentiation Molecular biology Erythropoietin receptor Repressor Proteins src-Family Kinases Gene Expression Regulation Suppressor of Cytokine Signaling 3 Protein Cell culture Protein Biosynthesis Mutation Ectopic expression sense organs Signal transduction Carrier Proteins psychological phenomena and processes Transcription Factors |
| Zdroj: | Oncogene. 22:3221-3230 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1206381 |
| Popis: | The SOCS family of genes are negative regulators of cytokine signalling with SOCS-1 displaying tumor suppressor activity. SOCS-1, CIS and SOCS-3 have been implicated in the regulation of red blood cell production. In this study, a detailed examination was conducted on the expression patterns of these three SOCS family members in normal erythroid progenitors and a panel of erythroleukemic cell lines. Unexpectedly, differences in SOCS gene expression were observed during maturation of normal red cell progenitors, viz changes to CIS were inversely related to the alterations of SOCS-1 and SOCS-3. Similarly, these SOCS genes were differentially expressed in transformed erythoid cells - erythroleukemic cells immortalized at an immature stage of differentiation expressed SOCS-1 and SOCS-3 mRNA constitutively, whereas in more mature cell lines SOCS-1 and CIS were induced only after exposure to erythropoietin (Epo). Significantly, when ectopic expression of the tyrosine kinase Lyn was used to promote differentiation of immature cell lines, constitutive expression of SOCS-1 and SOCS-3 was completely suppressed. Modulation of intracellular signalling via mutated Epo receptors in mature erythroleukemic lines also highlighted different responses by the three SOCS family members. Close scrutiny of SOCS-1 revealed that, despite large increases in mRNA levels, the activity of the promoter did not alter after erythropoietin stimulation; in addition, erythroid cells from SOCS-1-/- mice displayed increased sensitivity to Epo. These observations indicate complex, stage-specific regulation of SOCS genes during normal erythroid maturation and in erythroleukemic cells. |
| Databáze: | OpenAIRE |
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