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A selective switch from expression of Shc1 gene to Shc3 occurs with maturation of neuronal precursors into postmitotic neurons. Previous studies showed that in the embryo, Shc1 is maximally expressed in dividing CNS stem cells while it is silenced in mature neurons, where it is replaced by Shc3. Under normal conditions Shc3 is never expressed by glial cells. We now show that in human astrocytomas and glioblastomas, the normal pattern of expression of Shc1/Shc3 is totally subverted, both proteins being present at the same time and in the same cells. Our data indicate that Shc3 is maximally expressed, together with Shc1, in glioblastoma, a highly proliferative tumor with little, if any, indication of neuronal differentiation. In primary cultures of glioblastoma, tumor cells maintain Shc1 expression but downregulate Shc3. Analysis of the phosphorylation status of Shc3 in human glioblastoma tumor samples in vivo indicates that it is tyrosine phosphorylated. Finally, we found that the expression of truncated variants of Shc3 with dominant-negative effects in human high-grade glioma cells that maintain Shc3 expression in vitro leads to a decreased Akt posphorylation and increased apoptosis, thus resulting in impaired survival of the transfected cells. These data suggest that Shc molecules play an important role in glioblastoma cell growth and survival.Oncogene (2005) 24, 5198–5206. doi:10.1038/sj.onc.1208708; published online 2 May 2005 [ABSTRACT FROM AUTHOR]

EBP1 was identified as a protein that interacts with the ErbB-3 receptor and possibly contributes to transducing growth regulatory signals. The existence of EBP1 homologs across species from simple eukaryotes to humans and its wide tissue expression pattern suggest that EBP1 acts as a general signaling molecule. We provide evidence that EBP1 is localized to the cytoplasm and to the nucleolus, and that its nucleolar localization requires amino-acid sequences present at both the amino- and carboxy-terminus of the molecule. We also show that EBP1 overexpression inhibits proliferation of human fibroblasts, and that this effect is linked to its nucleolar localization. Using mass spectrometry we demonstrate that EBP1 is part of ribonucleoprotein complexes and associates with different rRNA species. It is becoming clear that cell growth and proliferation are actively coordinated with rRNA processing and ribosome assembly. Our findings indicate that EBP1 is a nucleolar growth-regulating protein, and we propose that it could represent a new link between ribosome biosynthesis and cell proliferation.Oncogene (2004) 23, 4454-4465. doi:10.1038/sj.onc.1207579 Published online 5 April 2004 [ABSTRACT FROM AUTHOR]