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Titolo:
STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells
Autore:
Nosaka, T; Kawashima, T; Misawa, K; Ikuta, K; Mui, ALF; Kitamura, T;
Indirizzi:
Univ Tokyo, Inst Med Sci, Dept Hematopoiet Factors, Minato Ku, Tokyo 1088639, Japan Univ Tokyo Tokyo Japan 1088639 Factors, Minato Ku, Tokyo 1088639, Japan Kyoto Univ, Fac Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan Kyoto Univ Kyoto Japan 6068501 Med Chem, Sakyo Ku, Kyoto 6068501, Japan Univ British Columbia, Vancouver Hosp & Hlth Sci Ctr, Jack Bell Res Ctr, Dept Surg, Vancouver, BC V6H 3Z6, Canada Univ British Columbia Vancouver BCCanada V6H 3Z6 ver, BC V6H 3Z6, Canada
Titolo Testata:
EMBO JOURNAL
fascicolo: 17, volume: 18, anno: 1999,
pagine: 4754 - 4765
SICI:
0261-4189(19990901)18:17<4754:SAAMRO>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
PIM-1 TRANSGENIC MICE; C-MYC; TRANSCRIPTIONAL ACTIVATION; TARGETED DISRUPTION; SIGNAL TRANSDUCERS; MYELOID-LEUKEMIA; GENE-EXPRESSION; LYMPHOMA-CELLS; LACKING JAK3; TH2 CELLS;
Keywords:
apoptosis; JAB; pim-1; p21(WAF1/Cip1); STAT5;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
71
Recensione:
Indirizzi per estratti:
Indirizzo: Kitamura, T Univ Tokyo, Inst Med Sci, Dept Hematopoiet Factors, Minato Ku,Tokyo 1088639, Japan Univ Tokyo Tokyo Japan 1088639 nato Ku, Tokyo 1088639, Japan
Citazione:
T. Nosaka et al., "STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells", EMBO J, 18(17), 1999, pp. 4754-4765

Abstract

Signal transducers and activators of transcription (STATs) play key roles in growth factor-mediated intracellular signal transduction, In the presentstudy using a constitutively active STAT5 mutant, we show that STAT5 has pleiotropic functions regulating cell proliferation, differentiation and apoptosis in an IL-3-dependent Ba/F3 cell line, The mutant STAT5 possessed constitutive tyrosine phosphorylation and DNA binding activity induced expression of bcl-xL. and pim-1 in the absence of IL-3 in Ba/F3 cells, and rendered Ba/F3 cells factor-independent. Unexpectedly, IL-3 treatment of the factor-independent Ba/F3 cells expressing the constitutively active STAT5 resulted in apoptosis within 24 h, or differentiation followed by cell death. In these cells, mRNA expression of growth inhibitory genes downstream of STAT5such as CIS, JAB/SOCS-1/SSI-1, and p21(WAF1/Cip1) was highly induced, correlating with prolonged hyper-phosphorylation of the mutant STAT5 after IL-3stimulation. Of the STAT5-regulated genes, we found that constitutive expression of JAB/SOCS-1/SSI-1 was sufficient to induce apoptosis of Ba/F3 cells, while p21(WAF1/Cip1) could induce differentiation of these cells. In contrast, constitutive expression of pim-1 nas sufficient to induce IL3-independent growth of Ba/F3 cells. These findings suggest that a single transcription factor regulates cell fate by varying the intensity and duration of the expression of a set of target genes.

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Documento generato il 22/01/20 alle ore 06:36:03