Identification of alternative protein partners of tumor suppressors from INK4 family

Project leader: Ján Markus
Project duration: 2009 - 2011

Proteins of the INK4 family play an important role in the regulation of cell cycle through the inhibition of Cdk4/6-Rb-E2F pathway. Although all 4 members of the family share the ability to inhibit the interaction of Cdk4 and Cdk6 with cyclin D, there is an emerging evidence that they have other functions. Besides the different tissue-specific expression of particular members, different INK4 genes are inactivated in different cancers and the proteins show various non Cdk4/6-associated activities. It was also shown that the INK4a/p16 interacts with at least one non-Cdk protein and participates on the regulation of cell proliferation through the c-Jun/JNK pathway. Aim of this project is to identify other interaction partners of p16 and other INK4 proteins that would allow to explain functional variability of the INK4 proteins. Results of this study will help to better understand the tumor suppressor capacities of INK4 members and to design more efficient therapies aimed at restoration of all their functions.

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