This Is MS Multiple Sclerosis Knowledge & Support Community

I'm noticing a lot of research abstracts mentioning p53 lately. I don't have a clue what it is, but if you look through old posts at ThisIsMS, you'll see some threads from OddDuck and BioDocFL talking a bit about it. I also just saw this abstract from last year from Vanderbilt and one of the oft-referenced researchers around here, Sriram.



Defective ATM-p53-mediated apoptotic pathway in multiple sclerosis.

Ann Neurol. 2005 Oct;58(4):577-84.
Deng X, Ljunggren-Rose A, Maas K, Sriram S.
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA. xinqing.deng@vanderbilt.edu

Defective elimination of autoreactive cells is thought to play a role in the development of autoimmune diseases including multiple sclerosis (MS).

We examined the activation of the ATM-CHK2-p53 pathway in MS patients after subjecting their peripheral blood mononuclear cells to gamma-irradiation. We found that peripheral blood mononuclear cells from a subset of MS patients show resistance to cell death induced by irradiation. This defect is due to impaired constitutive expression and activation of ATM (ataxia telangiectasia mutated), resulting in impaired stabilization of p53.

We predict that these fundamental defects likely alter the regulation of the immune population of cells in MS and may contribute to the development or progression of the disease.

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In general, p53 is a signaling protein which plays a role in stimulating apoptosis which is programmed cell death.

Here are a couple of links to research slides which briefly highlight the role that p53 plays in apoptosis. Note that lines in the diagrams that have arrow heads indicate a stimulatory pathway while lines which have flat bars at the end indicate an inhibitory pathway.

• The p53 Signaling Pathway
  The ATM/p53 Signaling Pathway
  Activation and Inhibition of Apoptosis

NHE

Thanks for those links. The last one caught my eye because some of the research I've seen talks about the ATM/Chk2/p53 pathway, which is shown on that slide. Interesting.

Dignan wrote:Thanks for those links.

It's good to hear that you found those slides helpful in understanding p53. Here's some more general information on p53 from another biochem supplier and this page has a link to an interactive p53 pathway diagram though I admit the last one is a bit overwhelming.

NHE