This was necessary since Hsp70 functionally collaborates and interacts, at least indirectly through Hop, with Hsp90. For newly synthesized proteins, the Hsp70 multicomponent machine tends to work upstream of Hsp90, and thus, in this context and others, intersections between these two molecular chaperone systems are expected. To demonstrate the usefulness and the power of Hsp90Int.db, we followed up on the prediction that Aha1 is involved in nucleocytoplasmic transport and were able to confirm it experimentally. Naturally, these results raise further questions. For example, the interplay of Aha1 and Hsp90 will need to be further clarified. Likewise, it will be interesting to investigate the generality of a role for Aha1 in nuclear import and its role in export. However, these early successes of Hsp90Int.db should suffice to incite researchers to explore Hsp90Int.db and/or to build a PPI for their own POI using our workflow. Supporting Information 9 October 2011 | Volume 6 | Issue 10 | e26044 The Hsp90 Interactome Acknowledgments We thank Manfredo Quadroni, Joel Walicki, ” and Katharina Strub for critical comments on the manuscript, and Pierre-Andre Briand for constructing plasmid pTom.GR. Author Contributions Conceived and designed the experiments: PCE AB BM DP. Performed the experiments: PCE AB BM. Analyzed the data: PCE AB BM DP. Contributed reagents/materials/Digitoxin chemical information analysis tools: PCE PD. Wrote the paper: DP. 10 October 2011 | Volume 6 | Issue 10 | e26044 The Hsp90 Interactome 56. Galigniana MD, Echeverria PC, Erlejman A, Piwien-Pilipuk G Role of molecular chaperones and TPR-domain proteins in the cytoplasmic transport of steroid receptors and their passage through the nuclear pore. Nucleus 1: 299308. 57. Freedman ND, Yamamoto KR Importin 7 and importin a/importin b are nuclear import receptors for the glucocorticoid receptor. Mol Biol Cell 15: 22762286. 58. Echeverria PC, Mazaira G, Erlejman A, Gomez-Sanchez C, Piwien Pilipuk G, et al. Nuclear import of the glucocorticoid receptor-Hsp90 complex through the nuclear pore complex is mediated by its interaction with Nup62 and importin b. Mol Cell Biol 29: 47884797. 59. Pratt WB, Toft DO Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 18: 306360. 60. Martin A, Ochagavia ME, Rabasa LC, Miranda J, Fernandez-de-Cossio J, et al. BisoGenet: a new tool for gene network building, visualization and analysis. BMC Bioinformatics 11: 91. 61. Hartl FU, Hayer-Hartl M Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295: 18521858. 62. Richter K, Haslbeck M, Buchner J The heat shock response: life on the verge of death. Mol Cell 40: 253266. 
11 October 2011 | Volume 6 | Issue 10 | e26044 Differentiation of Chronic Lymphocytic Leukemia B Cells into Immunoglobulin Secreting Cells Decreases LEF-1 Expression Albert Gutierrez Jr.1, Bonnie K. Arendt1, Renee C. Tschumper1, Neil E. Kay2, Clive S. Zent2, Diane F. Jelinek1 1 Department of Immunology, Mayo Graduate School, College of Medicine, Mayo Clinic, Rochester, Minnesota, United States of America, 2 Department of Internal Medicine, Mayo Graduate School, College of Medicine, Rochester, Mayo Clinic, Minnesota, United States of America Abstract Lymphocyte enhancer binding factor 1 plays 10866142” a crucial role in B lineage development and is only expressed in B cell precursors as B cell differentiation into mature B and plasma cells silences its expression. Chronic lymphocytic leukemia cells aberrant