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Hint2, a mitochondrial tumor suppressor

English title Hint2, a mitochondrial tumor suppressor
Applicant Dufour Jean-François
Number 112173
Funding scheme Project funding
Research institution Institut für Klinische Pharmakologie Universität Bern
Institution of higher education University of Berne - BE
Main discipline Physiology : other topics
Start/End 01.04.2006 - 31.03.2009
Approved amount 227'000.00
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Keywords (6)

mitochondria; apoptosis; conditional knock out; tumor suppressor; hepatocellular carcinoma; methylation

Lay Summary (English)

Lay summary
HIstidine triad NucleoTide-binding (HINT) proteins, are AMP-lysine hydrolases present in all forms of life, but still of uncertain biological function. Our research is focused on the characterization of Hint2. We have already shown that Hint2 is a novel type of mitochondrial apoptotic sensitizer downregulated in several common types of human tumors. In the proposed work we will study the phenotype of mice lacking Hint2 as well as lacking both Hint1 and Hint2. These experiments will provide critical information regarding the tumor suppressor role of Hint2. The mechanism leading to the downregulation of Hint2 in human cancers will be investigated by assessing the methylation of its promoter. We will take advantage of large scale technologies (proteomics) to identify the mitochondrial proteins whose expression is affected by Hint2. Based on the structure of the model compound we used as a substrate in vitro, it is possible that the enzymatic function of Hint2 is to remove AMP adducts linked to mitochondrial proteins, in particular to proteins of the respiratory chain. We designed experiments to test this hypothesis. Our findings will advance our understanding of HINT proteins and their role in mitochondria, and in broader terms, will add a new dimension to the study of tumor biology.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants


Associated projects

Number Title Start Funding scheme
125399 Hint1, Hint2, apoptosis and proliferation 01.04.2009 Project funding