Differential regulation of SOCS genes in normal and transformed erythroid cells.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print Cited Medium: Print ISSN: 0950-9232 (Print) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE

Publication: <2002->: Basingstoke : Nature Publishing Group
Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-

Repressor Proteins* ; Transcription Factors*; Carrier Proteins/*genetics ; Erythroid Precursor Cells/*metabolism ; Immediate-Early Proteins/*genetics ; Proteins/*genetics; Animals ; Carrier Proteins/biosynthesis ; Carrier Proteins/physiology ; Cell Differentiation ; Cell Line, Transformed ; Cells, Cultured ; Erythroid Precursor Cells/cytology ; Erythroid Precursor Cells/drug effects ; Erythropoietin/pharmacology ; Gene Expression Regulation ; Immediate-Early Proteins/biosynthesis ; Mice ; Mutation ; Promoter Regions, Genetic ; Protein Biosynthesis ; RNA, Messenger/biosynthesis ; Receptors, Erythropoietin/genetics ; Suppressor of Cytokine Signaling 1 Protein ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; Transcriptional Activation ; src-Family Kinases/metabolism

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.

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CA-77447 United States CA NCI NIH HHS; R01 CA077447-03 United States CA NCI NIH HHS; R37 CA022556 United States CA NCI NIH HHS; R01 CA022556 United States CA NCI NIH HHS; R01 CA077447-02 United States CA NCI NIH HHS; CA-22556 United States CA NCI NIH HHS

0 (Carrier Proteins)
0 (Immediate-Early Proteins)
0 (Proteins)
0 (RNA, Messenger)
0 (Receptors, Erythropoietin)
0 (Repressor Proteins)
0 (Socs1 protein, mouse)
0 (Socs3 protein, mouse)
0 (Suppressor of Cytokine Signaling 1 Protein)
0 (Suppressor of Cytokine Signaling 3 Protein)
0 (Suppressor of Cytokine Signaling Proteins)
0 (Transcription Factors)
0 (cytokine inducible SH2-containing protein)
11096-26-7 (Erythropoietin)
EC 2.7.10.2 (lyn protein-tyrosine kinase)
EC 2.7.10.2 (src-Family Kinases)

Date Created: 20030523 Date Completed: 20030616 Latest Revision: 20190508

20250114

PMC2396148

10.1038/sj.onc.1206381

12761492