| TNFα is a major contributor to muscle pathology which include cachexia as well as muscle atrophy during aging. TNFα illicits a wide range of responses which on one side involves cell death/cell differentiation and on the other side, cell proliferation. In muscle cells, all of these effects are possible and the regulation between these outcomes can determine the ability of muscle to differentiate, regenerate, or die. TNFα is novel because it is able to engage both cell death and cell survival pathways. Balance between these two divergent branches convey the final outcome. As such, understanding how the cell death and cell survival pathways intersect will further our ability to manipulate TNFα signaling in order to better our standard of living as in the case of TNFα-mediated muscle pathology. Furthermore, understanding how these two pathways are regulated in muscle will garner more insight into signal transduction. To this end we have also focused on a protein called PW1 which has been previously identified as a NFκB regulator within the TNFα pathway and a mediator of p53 induced apoptosis. We find that PW1 may modulate TNFα signaling in order to engage the cell death pathway in order to modulate differentiation. From this we can learn that the pathways which regulate cell death and cell differentiation may be more intertwined than previously recognized. |
