Ma, Jian

ASPP2 is an important tumor suppressor protein promoting p53‐dependent and‐independent apoptosis. However, it has been unclear how ASPP2 protein is regulated. Here, we identified Itch as the E3 ubiquitin ligase for ASPP2. Itch interacts with ASPP2 and mediates its degradation and ubiquitination in vivo. The PPXY motif of ASPP2 interacts with the WW domains of Itch. Yap1 competes with Itch for binding to ASPP2, and prevents Itch‐mediated degradation and ubiquitination of ASPP2. Together, these observations reveal that Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability through competing post‐translational regulatory mechanism of ASPP2.

Abstract Chromosome rearrangements that result in gene fusions have important roles in the initial steps of tumorigenesis especially in leukemias and lymphomas, but the biological and clinical impact of gene fusions in the common solid tumor has been less appreciated. We previously generated RNAseq data from 12 oropharyngeal tumors along with matched normal tissue from the same patients. We utilized and compared two bioinformatic pipelines, SnowShoes-FTD and FusionHunter to identify two novel fusion events involving of MGST3-ZMAT5 and MS4A7-DKFZp586P0123. These fusions were validated utilizing. Reverse transcriptase polymerase chain reaction (RT-PCR) and Sanger sequencing validated. In the first translocation the 5′ UTR of MGST3 was fused with exon 1 of ZMAT5, and in the second translocation the exon 2 of MS4A7 was fused with 3′ UTR of DKFZp586P0123. These precise fusions were not present in the matched normal tissue, however, they were only found in the single tumor in which they were identified. Given a growing and powerful set of high-throughput massively parallel sequencing technologies, the future for genome-wide analysis of chromosome rearrangement appears open in many directions. Ultimately, we hope that this integrative methodology will elucidate key aspects of tumor biology as well as generate novel targets for cancer diagnostics and therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3100. doi:1538-7445.AM2012-3100

Abstract Motivation: Fusion transcripts can be created as a result of genome rearrangement in cancer. Some of them play important roles in carcinogenesis, and can serve as diagnostic and therapeutic targets. With more and more cancer genomes being sequenced by next-generation sequencing technologies, we believe an efficient tool for reliably identifying fusion transcripts will be desirable for many groups. Results: We designed and implemented an open-source software tool, called FusionHunter, which reliably identifies fusion transcripts from transcriptional analysis of paired-end RNA-seq. We show that FusionHunter can accurately detect fusions that were previously confirmed by RT-PCR in a publicly available dataset. The purpose of FusionHunter is to identify potential fusions with high sensitivity and specificity and to guide further functional validation in the laboratory. Availability: http://bioen-compbio.bioen.illinois.edu/FusionHunter/. Contact: jianma@illinois.edu Supplementary information: Supplementary data are available at Bioinformatics online.