Volume 10 Supplement 2

Breast Cancer Research 2008

Open Access

Proapoptotic protein Bid is regulated by phosphorylation during anoikis and the cell cycle

  • J Lindsay1 and
  • AP Gilmore1
Breast Cancer Research200810(Suppl 2):P44

https://doi.org/10.1186/bcr1928

Published: 13 May 2008

Adhesion to the extracellular matrix is fundamental in cell survival, proliferation and differentiation. In the absence of correct signals from the extracellular matrix, normal cells die by a form of apoptosis termed anoikis. These mechanisms are abrogated in invasive breast cancer. The BH3-only protein Bid is involved in anoikis. The full-length protein translocates to the mitochondria following cell detachment from the matrix and this is not dependent on Bid cleavage by caspase 8. Understanding the regulation of full-length Bid during apoptosis will help identify ways to manipulate the apoptotic machinery to prevent cell survival during metastasis. Bid can be phosphorylated following a number of stimuli. We have shown that Bid becomes dephosphorylated in epithelial cells undergoing anoikis. We have also identified Bid as being phosphorylated during normal cell cycle. Arresting the cell cycle at results in accumulation of nonphosphorylated Bid. G1/S Conversely, arresting cells during mitosis results in an increase in the phosphorylated form of Bid. Mutant forms of the protein in which potential phosphorylation sites were removed were used to identify serine 66 as a critical site of phosphorylation. Inhibition of the cell cycle kinase cdk1 in fibroblasts blocks Bid phosphorylation and is therefore a potential regulatory kinase acting to control Bid during the cell cycle. Our results indicate a novel site of regulation in Bid at serine 66. This residue is phosphorylated during mitosis and may act to control the sensitivity to apoptosis during this part of the cell cycle.

Authors’ Affiliations

(1)
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester

Copyright

© BioMed Central Ltd 2008

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