an atlas of altered expression of deubiquitinating enzymes in human cancer改变表达式的atlas deubiquitinating酶在人类癌症.pdfVIP

An Atlas of Altered Expression of Deubiquitinating Enzymes in Human Cancer 1 1 2 2 1 Chiara Luise , Maria Capra , Maddalena Donzelli , Giovanni Mazzarol , Maria Giovanna Jodice , Paolo 1 2,3 1,2,3 1 Nuciforo , Giuseppe Viale , Pier Paolo Di Fiore *, Stefano Confalonieri * 1 IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy, 2 Istituto Europeo di Oncologia, Milan, Italy, 3 Dipartimento di Medicina, Chirurgia e Odontoiatria, ` Universita degli Studi di Milano, Milan, Italy Abstract Background: Deubiquitinating enzymes (DUBs) are proteases that process ubiquitin (Ub) or ubiquitin-like gene products, remodel polyubiquitin(-like) chains on target proteins, and counteract protein ubiquitination exerted by E3 ubiquitin- ligases. A wealth of studies has established the relevance of DUBs to the control of physiological processes whose subversion is known to cause cellular transformation, including cell cycle progression, DNA repair, endocytosis and signal transduction. Altered expression of DUBs might, therefore, subvert both the proteolytic and signaling functions of the Ub system. Methodology/Principal Findings: In this study, we report the first comprehensive screening of DUB dysregulation in human cancers by in situ hybridization on tissue microarrays (ISH-TMA). ISH-TMA has proven to be a reliable methodology to conduct this kind of study, particularly because it allows the precise identification of the cellular origin of the signals. Thus, signals associated with the tumor component can be dis