Protein Linked To Bone Marrow Failure In Humans Found Through Study Of Dark-skinned Mice (7/20/08)
McGowan, Barsh, and their colleagues found that skin from the feet of the mutant mice exhibited elevated levels of p53. This elevation, or "activation," of p53 stimulated the production of a protein called Kit ligand that stimulates the growth of pigment cells, which turned the mice's skin darker than normal. In contrast, mutant mice unable to express p53 had normal levels of Kit ligand. They also had light-colored feet and unaffected numbers of red blood cells. ...
The researchers hypothesize that increased activation of p53 affects different types of cells in the body in different ways. In skin cells, it increases the amount of Kit ligand and causes darker skin, whereas in bone marrow cells it causes anemia by causing the death of red blood cell precursors.
Is there some lesson in this? Well, p53 is generally regarded as a "good" protein, because it helps ward off cancer that would otherwise result from DNA damage. But it does this by promoting apoptosis of cells affected by the DNA mutation. Anemia is the result when too many red blood cells die.
And the skin darkening? Earlier studies indicate that is also a side effect of increased levels of p53. Such unexpected – and not always desirable – side effects are the reason that developing drugs to treat disease is so difficult. There is so much unexpected interconnection of our cellular machinery, adjusting something in one place can lead to problems in quite different places.
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