p120-v-Abl expression overcomes TGF-β1 negative regulation of c-myc transcription but not cell growth

Maria C. Birchenall-Roberts, Seong J. Kim, Daniel C. Bertolette, Jennifer M. Turley, Tao Fu, Ok S. Bang, James J. Kasper, Young Do Yoo, Francis W. Ruscetti

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Abstract

Transformation of interleukin-3 dependent (IL-3) 32D-123 myeloid cells by p120-v-Abl produced the factor-independent 32D-abl cell line. In 32D-abl cells, myc expression was found to be significantly higher than in the parental cells and was correlated with increased E2F-1 protein expression and DNA binding ability. Surprisingly, in 32D-abl cells, TGF-β1, a potent G1/S inhibitor of 32D-123 and 32D-abl cell growth, increased E2F transactivation as shown by increased c-myc promoter-CAT and GAL4-E2F-1 activity. In addition, TGF-β1 was also found to increase E2F-1 protein levels but had no effect on steady-state retinoblastoma (RB) protein levels or phosphorylation state. In the absence of TGF-β1, transient expression of RB in v-Abl expressing cells resulted in decreased c-myc transcription, inhibition of GAL4-E2F-1 driven transactivation and inhibition of cellular proliferation. RB and v-Abl were found to physically asssociate in vivo and in vitro via v-Abl's ATP binding region. In summary, these studies established that in myeloid cells: (1) v-Abl binds RE resulting in increased E2F-1-driven c-myc transcription, and (2) an alternative pathway exists for TGF-β1-mediated growth inhibition of v-Abl-transformed cells, in which increased rather than decreased E2F-mediated c-myc transcription is observed.

Original languageEnglish
Pages (from-to)1499-1509
Number of pages11
JournalOncogene
Volume13
Issue number7
Publication statusPublished - 1996 Nov 2
Externally publishedYes

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Keywords

  • c-myc
  • E2F-1
  • RB
  • TGF-β1
  • v-Abl

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Birchenall-Roberts, M. C., Kim, S. J., Bertolette, D. C., Turley, J. M., Fu, T., Bang, O. S., Kasper, J. J., Yoo, Y. D., & Ruscetti, F. W. (1996). p120-v-Abl expression overcomes TGF-β1 negative regulation of c-myc transcription but not cell growth. Oncogene, 13(7), 1499-1509.