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Exploring ubiquitin <strong>signaling</strong> with dedicated PIQOR Ubiquitin-PS microarrays<br />

Hartmut Scheel, Corinna B. Scholz, Kay Hofmann<br />

Bioinformatics Group, Miltenyi Biotec GmbH, MACSmolecular Business Unit,<br />

Stöckheimer Weg 1, D-50829 Köln, Germany. E-mail: kay.hofmann@miltenyibiotec.de<br />

The MACSmolecluar business unit of Miltenyi Biotec offers smart products <strong>and</strong> services for<br />

molecular biology research <strong>and</strong> gene expression analysis via the proprietary PIQOR<br />

Microarray platform for topic-defined or custom expression profiling solutions.<br />

Here, we introduce the PIQOR Ubiquitin-PS microarray with a focus on the ubiquitinproteasome<br />

system (UPS). By developing this microarray, we are addressing the growing<br />

need for a deeper underst<strong>and</strong>ing of the UPS <strong>and</strong> a comprehensive monitoring of its<br />

components. It has become clear in the recent years that ubiquitylation plays a key role in<br />

processes like cell cycle progression, protein quality control, DNA repair, stress response,<br />

apoptosis <strong>and</strong> regulation of <strong>signaling</strong>.<br />

The importance of the UPS for signal transduction is not restricted to its well-known role in<br />

the selective degradation of regulatory proteins. Equally important is the role of ubiquitin<br />

modification as a signal by itself. The high complexity of the UPS is underscored by the large<br />

number of components involved in ubiquitin attachment, removal <strong>and</strong> recognition, all similar<br />

to the numbers known for phosphorylation <strong>signaling</strong>. A deregulation of the UPS is associated<br />

with a multitude of diseases, including cancer, catabolic diseases, inflammation <strong>and</strong><br />

neurodegeneration. Therefore, the UPS becomes more <strong>and</strong> more a rich s<strong>our</strong>ce for discoveries<br />

with therapeutic impact <strong>and</strong> ubiquitin research increases steadily.<br />

A hallmark of the UPS is that most proteins involved belong to a limited number of protein<br />

families characterized by common homology domains. The bioinformatics group of Miltenyi<br />

MACSmolecular possesses appropriate tools like the profile technique to mine sequence<br />

databases for proteins with a given homology domain. In a systematic UPS analysis<br />

programme applying this technique, a list of ~1200 genes was generated covering all aspects<br />

of the UPS <strong>and</strong> including many unpublished c<strong>and</strong>idate genes, e.g. approximately 600 E3<br />

ligases were identified. With this catalogue of genes at h<strong>and</strong>, a new microarray was designed,<br />

which allows the systematic detection of mRNA expression changes in the entire UPS. This<br />

new microarray fits nicely into the portfolio of other topic-defined microarrays offered by<br />

Miltenyi Biotec, which already includes microarrays designed for oncology <strong>and</strong> immunology.<br />

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