A scientific team led by WEHI’s Professor Andreas Strasser and Dr Thomas Kaufmann has established that, contrary to a recent high-profile study, the protein Bid does not have any special role in a cell’s response to DNA damage or replicative stress.

In response to such stresses, damaged cells are normally removed by cell suicide (apoptosis). This ability to self-destruct is an important part of our body’s defence against accumulating damaged cells, which if long-lived can become dangerous cancer cells.

Although Bid has been long recognised as a cell death-inducing protein involved in certain liver pathologies, evidence has been published in the journal Cell that Bid has a second function: namely, to regulate cell cycle arrest, which is typically induced after DNA-damage or replicative stress.

The WEHI team created Bid “knockout” mice (which cannot express the Bid protein) and found that cells from these mice underwent cell cycle arrest and apoptosis as usual in response to DNA-damage or replicative stress. This is definitive evidence that Bid is dispensable for DNA damage-induced cell death and cell cycle arrest.

This finding has important implications for cancer research and therapy, since many chemotherapeutic drugs and radiation kill cancer cells via a DNA-damage response.

The research team led by Andreas Strasser comprises Thomas Kaufmann, Lin Tai, and David Huang at WEHI, who collaborated with Paul Ekert, Fiona Norris, Ralph Lindemann and Ricky Johnstone and Vishva Dixit from the Royal Children’s Hospital (Melbourne), VGS Pathology (Melbourne), the Peter MacCallum Cancer Centre (Melbourne) and Genentech (South San Francisco, CA USA).

This work was generously funded by grants and fellowships from the NHMRC (Canberra), the NCI (NIH, USA), the Leukemia and Lymphoma Society of America, the JDRF/NHMRC, the Cancer Council Victoria, the Leukemia Foundation of Australia, the Swiss National Science Foundation, the Roche Research Foundation (Switzerland), the Novartis Foundation (Switzerland) and by a Pfizer Australia Senior Research Fellowship.

The team’s findings were published in the journal Cell on 20 April 2007.