A stepwise and digital pattern of RSK phosphorylation determines the outcome of thymic selection.

Developing CD4CD8 double-positive (DP) thymocytes with randomly generated T cell receptors (TCRs) undergo positive (maturation) or negative (apoptosis) selection on the basis of the strength of TCR stimulation. Selection fate is determined by engagement of TCR ligands with a subtle difference in affinity, but the molecular details of TCR signaling leading to the different selection outcomes have remained unclear. We performed phosphoproteome analysis of DP thymocytes and found that p90 ribosomal protein kinase (RSK) phosphorylation at Thr was induced specifically by high-affinity peptide ligands.

Targeting chemoresistance in Xp11.2 translocation renal cell carcinoma using a novel polyamide-chlorambucil conjugate.

Renal cell carcinoma with Xp11.2 translocation involving the TFE3 gene (TFE3-RCC) is a recently identified subset of RCC with unique morphology and clinical presentation. The chimeric PRCC-TFE3 protein produced by Xp11.

Blood and lymphatic systems are segregated by the FLCN tumor suppressor.

Blood and lymphatic vessels structurally bear a strong resemblance but never share a lumen, thus maintaining their distinct functions. Although lymphatic vessels initially arise from embryonic veins, the molecular mechanism that maintains separation of these two systems has not been elucidated. Here, we show that genetic deficiency of Folliculin, a tumor suppressor, leads to misconnection of blood and lymphatic vessels in mice and humans.

TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease.

Renal cell carcinoma (RCC) associated with Xp11.2 translocation (TFE3-RCC) has been recently defined as a distinct subset of RCC classified by characteristic morphology and clinical presentation. The Xp11 translocations involve the TFE3 transcription factor and produce chimeric TFE3 proteins retaining the basic helix-loop-helix leucine zipper structure for dimerization and DNA binding suggesting that chimeric TFE3 proteins function as oncogenic transcription factors.

Determination of topological structure of ARL6ip1 in cells: identification of the essential binding region of ARL6ip1 for conophylline.

Conophylline (CNP) has various biological activities, such as insulin production. A recent study identified ADP-ribosylation factor-like 6-interacting protein 1 (ARL6ip1) as a direct target protein of CNP. In this study, we revealed that ARL6ip1 is a three-spanning transmembrane protein and determined the CNP-binding domain of ARL6ip1 by deletion mutation analysis of ARL6ip1 with biotinyl-amino-CNP.