January 11, 2005
Cancer, P53, and apoptosis - Meet BruceTopics: Medicine
Before you non-medical types go scurring to the next post, take a second or two and check this item out. Why should you be interested in apoptosis? If you have cancer or know someone who has cancer, you should care. Apoptosis is programmend cell death, a normal process except for cancer cells. P53 is a tumor suppressor gene that through it's transcriptional activity regulates the mitochondrial pathway of apoptosis. An Assistant Investigator at the Stowers Institute now provides us a clue about a gene that encodes a protein that inhibits p53 activation. More Bruce, less p53 activity and less tumor suppression, less bruce - more p53 activity and greater tumor suppression via activation of genes including Pidd, Bax, and Bak. These in turn activate mitochondria, leading to apoptosis - bingo, more tumor cells die. In other words, you should care.
From the actual abstract of the research article we learn that Chunying Du, Ph D:
(...) showed that deletion of the C-terminal half of Bruce, including the UBC domain, causes activation of caspases and apoptosis in the placenta and yolk sac, leading to embryonic lethality. This apoptosis is associated with up-regulation and nuclear localization of the tumor suppressor p53 and activation of mitochondrial apoptosis, which includes up-regulation of Bax, Bak, and Pidd, translocation of Bax and caspase-2 onto mitochondria, release of cytochrome c and apoptosis-inducing factor, and activation of caspase-9 and caspase-3. -end item
Here's the full layman's version in Medical News Today:
Chunying Du, Ph D, Assistant Investigator at the Stowers Institute, has published findings that reveal a previously unknown pathway of Bruce, the gene encoding a protein that inhibits apoptosis, or programmed cell death.
The findings are available online at http://www.pnas.org/cgi/reprint/0408744102v1 and will be published in the Jan. 18 issue of Proceedings of the National Academy of Sciences (PNAS).
Bruce has long been recognized as an inhibitor of apoptosis, but until now, its method of inhibition was not clear. Dr. Du analyzed Bruce mutant mice and found that Bruce regulates p53, a tumor suppressor gene, and the mitochondrial pathway of apoptosis.
Bruce's primary function resides upstream of mitochondria. Loss of function of Bruce increases the level of p53, making cells more sensitive to apoptosis. The transcriptional activity of p53 is responsible for the activation of genes including Pidd, Bax, and Bak. These in turn activate mitochondria, leading to apoptosis. Read more... -end item
While we are on the issue of p53 and cancer (and type-2 diabetes and aging), you may want to read about recent information on tumour suppressor gene PTEN which is, next to p53, the second most frequently mutated gene in human cancers..
Posted by Hyscience at January 11, 2005 10:41 AM
This is ANOTHER reason I read you... thanks for the great updates on cancer research, etc.!!!
Posted by: Beth at January 11, 2005 10:38 PM
That's an interesting development. I have long thought that p53 and apoptosis were very promising in the treatment of CA. Has there been any advances in vivo, beside rodents?
Posted by: Scott B at January 11, 2005 11:34 PM
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- Cancer, P53, and apoptosis - Meet Bruce - Jan 11, 2005