Rigorous in vivo serial passaging experiments will be required to determine if MSC influence the cancer stem cell population. The possibility that c-Myc may exert its effect upon DNA SCH772984 replication though alteration of chromatin structure is intriguing in light of the role of c-Myc in recruiting histone acetylase complexes and its direct binding to known replication origins. For example, studies in Drosophila have shown that tethering histone acetylases to chromatin increases origin activity. Finally, the finding that c-Myc sensitizes cells to replicationstress indicates that replication-coupled DNA repair might represent an Achilles’ heel of c-Myc-driven tumors to which new therapeutic approaches might be developed. Promoted by the encouraging results of MCAT transgenic mice, we set out to test whether body-wide delivery of MCAT by an AAV vector can improve exercise performance in normal mice. We have previously shown that AAV-9 is capable of whole body muscle transduction. Systemic Sclerosis is a complex inflammatory autoimmune disease characterized by excessive deposition of matrix molecules, leading to fibrosis of multiple organs including the skin, lungs, heart and gastrointestinal tract, and often leading to severe morbidity and premature death. Although the role of immune dysfunction in the pathogenesis of SSc is generally accepted, the exact pathways that cause immune dysfunction in SSc remain to be elucidated. Alterations in cellular immunity are typified by aberrant T cell biology both in the skin as well as circulation of SSc patients. For example, CD4+ T cells are increased in the circulation of SSc patients whereas NKT cells and c/d T cells are decreased. In addition, lesional skin from SSc patients displays various features consistent with T cell activation. To this end, we engineered MCAT in an AAV-9 vector and injected into the circulation of newborn BL6 mice. As expected, we observed widespread but mosaic MCAT expression in the heart and skeletal muscle. Similar to previous reports in MCAT transgenic mice, we did not see any detrimental effect on the growth rate and body weight in AV.RSV.MCAT infected mice. Accordingly, our present results strongly suggest that the NLS region of the receptor is the nucleolin-binding domain. Using the DTK ErbB1 mutant we demonstrated that the tyrosine kinase domain, although not essential for ErbB1/nucleolin interaction, is crucial for ErbB1 activation induced by nucleolin. Our results further indicate that DTK undergoes EGF or nucleolin induced dimerization but not phosphorylation indicating that nucleolinmediated receptor activation depends on the receptor kinase domain activity. Further examination of the nucleolin domains responsible for this interaction and for receptor activation was performed. We found that the C-terminal 212 amino acids of nucleolin are necessary for the interaction between nucleolin and ErbB4 or ErbB1.