California Institute of Technology

Johannes Graumann

Raymond J Deshaies

Gabriela Alexandru

Hypoxia, a state of lower than normal tissue oxygen tension, has recently been implicated in a host of human diseases, including cancer, heart disease, and neurological disorders. Novel associations between p97 and other proteins, including UBX-domain-containing proteins (UBX-polypeptides), HIF1&#x3b1;, and a variety of E3 ligases are provided herein. The disclosure provides complexes comprising UBX-domain-containing polypeptides (UBX-polypeptides) and other polypeptides involved in the degradation of ubiquitinated proteins. In addition, the disclosure provides uses for active agents that modulate protein-protein complex formation between an UBX-polypeptide and its complementary-binding substrate. For example, the disclosure provides methods for treating or preventing hypoxia-related disorders or conditions in a patient or a cell by administration of an active agent that modulates the activity of an UBX-polypeptide and/or its complementary binding-substrate. Furthermore, the disclosure provides uses for active agents that modulate HIF1&#x3b1; activity; such agents may be used to modulate processes that are regulated by HIF1&#x3b1;. The disclosure also provides many screening assays to identify test agents that modulate complex formation between an UBX-polypeptide and its complementary-binding substrate or methods for evaluating modes of action and/or effects of active agents that have already been identified as modulators of an UBX-polypeptide and/or its complementary-binding substrate.

Growing community of inventors

Munich, Georgia

Johannes Graumann