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Related Experiment Videos

Signaling by ABL oncogenes through cyclin D1

D E Afar1, J McLaughlin, C J Sherr

  • 1Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 10, 1995
PubMed
Summary

Oncogenic signals promote cell growth by disrupting the cell cycle. Cyclin D1 works with ABL oncogenes, suggesting a retinoblastoma protein-dependent pathway is key for cancer development.

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Area of Science:

  • Cellular biology
  • Cancer research
  • Molecular oncology

Background:

  • Oncogenic signals drive cellular proliferation by dysregulating the cell division cycle.
  • Cyclin D1 is a key regulator of G1-phase progression in the cell cycle.
  • ABL oncogenes are implicated in cellular transformation and cancer development.

Purpose of the Study:

  • To investigate the synergistic role of Cyclin D1 and ABL oncogenes in cellular transformation.
  • To elucidate the role of the retinoblastoma protein in ABL oncogene-mediated mitogenic effects.
  • To determine if Cyclin D1 can rescue signaling-defective BCR-ABL mutants.

Main Methods:

  • Cell culture experiments involving fibroblasts and hematopoietic cells.
  • Analysis of Cyclin D1 binding to the retinoblastoma protein via a specific motif.

Related Experiment Videos

  • In vivo studies assessing malignant tumor formation.
  • Rescue experiments using a src-homology 2 (SH2) domain mutant of BCR-ABL.

    • Main Results:

    • Cyclin D1 synergizes with ABL oncogenes to transform cells in culture.
    • Synergy between Cyclin D1 and v-Abl depends on a motif mediating retinoblastoma protein binding.
    • Overexpression of Cyclin D1, but not Cyclin E, rescued a signaling-defective BCR-ABL mutant.
    • Cyclin D1 facilitated malignant tumor formation in vivo.

    Conclusions:

    • ABL oncogenes may exert mitogenic effects through a retinoblastoma protein-dependent pathway.
    • Cyclin D1 provides essential signals for malignant transformation in conjunction with activated tyrosine kinases.
    • Cyclin D1 is a critical factor in oncogene-induced cellular proliferation and tumorigenesis.