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Transforming growth factor-beta 1 induces apoptosis independently of p53 and selectively reduces expression of Bcl-2 in multipotent hematopoietic cells.
J Biol Chem 2000; 275(50):39137-45JB

Abstract

Transforming growth factor-beta1 (TGF-beta1) can inhibit cell proliferation or induce apoptosis in multipotent hematopoietic cells. To study the mechanisms of TGF-beta1 action on primitive hematopoietic cells, we used the interleukin-3 (IL-3)-dependent, multipotent FDCP-Mix cell line. TGF-beta1-mediated growth inhibition was observed in high concentrations of IL-3, while at lower IL-3 concentrations TGF-beta1 induced apoptosis. The proapoptotic effects of TGF-beta1 occur via a p53-independent pathway, since p53(null) FDCP-Mix demonstrated the same responses to TGF-beta1. IL-3 has been suggested to enhance survival via an increase in (antiapoptotic) Bcl-x(L) expression. In FDCP-Mix cells, neither IL-3 nor TGF-beta1 induced any change in Bcl-x(L) protein levels or the proapoptotic proteins Bad or Bax. However, TGF-beta1 had a major effect on Bcl-2 levels, reducing them in the presence of high and low concentrations of IL-3. Overexpression of Bcl-2 in FDCP-Mix cells rescued them from TGF-beta1-induced apoptosis but was incapable of inhibiting TGF-beta1-mediated growth arrest. We conclude that TGF-beta1-induced cell death is independent of p53 and inhibited by Bcl-2, with no effect on Bcl-x(L). The significance of these results for stem cell survival in bone marrow are discussed.

Authors+Show Affiliations

Leukaemia Research Fund Cellular Development Unit, Department of Biomolecular Sciences, UMIST, Sackville St., Manchester, M60 1QD, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10993901

Citation

Francis, J M., et al. "Transforming Growth Factor-beta 1 Induces Apoptosis Independently of P53 and Selectively Reduces Expression of Bcl-2 in Multipotent Hematopoietic Cells." The Journal of Biological Chemistry, vol. 275, no. 50, 2000, pp. 39137-45.
Francis JM, Heyworth CM, Spooncer E, et al. Transforming growth factor-beta 1 induces apoptosis independently of p53 and selectively reduces expression of Bcl-2 in multipotent hematopoietic cells. J Biol Chem. 2000;275(50):39137-45.
Francis, J. M., Heyworth, C. M., Spooncer, E., Pierce, A., Dexter, T. M., & Whetton, A. D. (2000). Transforming growth factor-beta 1 induces apoptosis independently of p53 and selectively reduces expression of Bcl-2 in multipotent hematopoietic cells. The Journal of Biological Chemistry, 275(50), pp. 39137-45.
Francis JM, et al. Transforming Growth Factor-beta 1 Induces Apoptosis Independently of P53 and Selectively Reduces Expression of Bcl-2 in Multipotent Hematopoietic Cells. J Biol Chem. 2000 Dec 15;275(50):39137-45. PubMed PMID: 10993901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transforming growth factor-beta 1 induces apoptosis independently of p53 and selectively reduces expression of Bcl-2 in multipotent hematopoietic cells. AU - Francis,J M, AU - Heyworth,C M, AU - Spooncer,E, AU - Pierce,A, AU - Dexter,T M, AU - Whetton,A D, PY - 2000/9/20/pubmed PY - 2001/3/3/medline PY - 2000/9/20/entrez SP - 39137 EP - 45 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 275 IS - 50 N2 - Transforming growth factor-beta1 (TGF-beta1) can inhibit cell proliferation or induce apoptosis in multipotent hematopoietic cells. To study the mechanisms of TGF-beta1 action on primitive hematopoietic cells, we used the interleukin-3 (IL-3)-dependent, multipotent FDCP-Mix cell line. TGF-beta1-mediated growth inhibition was observed in high concentrations of IL-3, while at lower IL-3 concentrations TGF-beta1 induced apoptosis. The proapoptotic effects of TGF-beta1 occur via a p53-independent pathway, since p53(null) FDCP-Mix demonstrated the same responses to TGF-beta1. IL-3 has been suggested to enhance survival via an increase in (antiapoptotic) Bcl-x(L) expression. In FDCP-Mix cells, neither IL-3 nor TGF-beta1 induced any change in Bcl-x(L) protein levels or the proapoptotic proteins Bad or Bax. However, TGF-beta1 had a major effect on Bcl-2 levels, reducing them in the presence of high and low concentrations of IL-3. Overexpression of Bcl-2 in FDCP-Mix cells rescued them from TGF-beta1-induced apoptosis but was incapable of inhibiting TGF-beta1-mediated growth arrest. We conclude that TGF-beta1-induced cell death is independent of p53 and inhibited by Bcl-2, with no effect on Bcl-x(L). The significance of these results for stem cell survival in bone marrow are discussed. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/10993901/Transforming_growth_factor_beta_1_induces_apoptosis_independently_of_p53_and_selectively_reduces_expression_of_Bcl_2_in_multipotent_hematopoietic_cells_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=10993901 DB - PRIME DP - Unbound Medicine ER -