Gene p73 regulation of cell death
The phenomenon apoptosis is a crucial factor in the treatment of cancer. Tumours that are resistant to radiation or chemotherapy are found to have their apoptotic pathways blocked. Some tumours however are highly responsive to treatment and their apoptotic pathways are active. This study investigated the role of gene p73 in the induction of cell death. p73 was found to regulate proteins Bax and PUMA, both of which are instrumental in cell death. This all-important gene also controls the CD95 pathway for apoptosis. There are two forms of p73, TA and DN and their different roles have been analysed and described. Basically, the TA isoform induces cell death while the DN isoform is anti-apoptotic. Furthermore, there are molecules that interact with p73 and therefore regulate its activity. One important candidate is Itch, an enzyme that specifically binds p73, but not a close relative, gene p53. A regulatory mechanism when DNA damage occurs comes into play as Itch is then down regulated and p73 levels increase. Another molecule involved in the apoptosis mechanism is PIAS-1. Its overall effect is to bind to p73 limiting its ability to undergo transcription. Furthermore, this study has also provided an explanation for the presence of multiple copies of chromosomes, or polyploidy, in tumours that exhibit over-expression. This involves the molecule, Bub-1 that binds to the pro-apoptotic form of the gene, TAp73. Finally, FLASH, a molecule that is part of the Cajal Bodies (CBs) in the nucleus, was found to interact with p73 and this in turn affects cell cycle progression. The mechanisms involved in apoptosis and tumour control are complex. Elucidating the intricacies of these pathways and their molecular control will help to point the way to new cancer therapies.
