MAY 29, 2014 12:00 PM PDT

Navigating the Complexities of the Human Oncoproteome with the SigNET KnowledgeBank

Speaker
  • Professor, Department of Medicine, University of British Columbia, President & Chief Scientific Officer, Kinexus Bioinformatics Corporation
    BIOGRAPHY

Abstract

The human genome encodes ~21,500 proteins that are subject to reversible phosphorylation at nearly 1 million phosphosites by about 538 protein kinases and 156 protein phosphatases. Amongst other regulatory proteins, these classes of proteins play a central role in cancer as oncoproteins (OP), tumour-requiring proteins (TRP) or tumour suppressor proteins (TSP). They can be distinguished in part by their mutation patterns across thousands of tumour specimens. OP feature highly restricted mutations that produce a gain of function, commonly by loss of repression by inhibitory domains or mimicry of activating phosphorylation sites with acid amino acid residue substitutions. TSP typically feature an extensive range of mutation types and locations in their genes, which lead to their loss of function. By contrast, TRP display extremely low rates of mutation in human cancers, about 5 to 10-fold lower that the background mutation rates evident in bystander genes. TRP may serve as ideal targets for cancer drug development as they may be more commonly required for cancer development than OP, and they may be less tolerant to mutations that facilitate drug resistance. Interestingly, many OP are down-regulated and TSP are up-regulated in their protein levels in human tumours, which indicates that intracellular regulatory networks typically evoke compensatory mechanisms to restore growth control or induce apoptosis. Therefore, gene expression and mutation data has to be interpreted in the context of integrated signalling pathways. The open-access, on-line suite of SigNET KnowledgeBases offered by Kinexus provide extensive known and predictive information of human proteins, their gene expression, interactions and phosphorylation, and in the case of protein kinases, drug interactions. The new OncoNET website (www.onconet.ca) is a repository of detailed information about the mRNA expression and mutation patterns for nearly 3000 genes linked to diverse types of human cancers.


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MAY 29, 2014 12:00 PM PDT

Navigating the Complexities of the Human Oncoproteome with the SigNET KnowledgeBank


Specialty

Research And Development

Gene Expression

Dna

Big Data

Cancer Research

Tumor

Biomarkers

Cancer

Earth Science

Oncology

University

Gene Sequencing

Drug Discovery

Mass Cytometry

Cell Culture

Geography

Asia50%

Europe50%

Registration Source

Website Visitors100%

Job Title

Student50%

Medical Laboratory Technician50%

Organization

Manufacturer - Other50%

Academic Institution50%


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