In collaboration with Prof. Silvia Soddu (Istituto Regina Elena, IRE) and Dr. Cinzia Rinaldo (IBPM-CNR) we are studying the structure and the function of the multidomain nuclear serine/threonine kinase HIPK2 (Homeodomain Interacting Protein Kinase 2) and its functional complexes.

HIPK2 plays an important role as tumor suppressor in malignant progression of many cancer types (colorectal, breast, skin, lung, liver, pancreas and others).

We demonstrated that a specific posttranslational modification that controls the dual-specific activity of HIPK2 affects the oligomerization state of the kinase domain and its stability, and it triggers structural modifications at the regulating substrate binding site that are energetically coupled to changes at the catalytic ATP-binding pocket.

We are currently working on the full-length HIPK2 in complex with pro-apoptotic functional partners with the key goal to provide relevant structural and functional information exploitable for applications in cancer therapies.

Main Publications

Effects of Y361-auto-phosphorylation on structural plasticity of the HIPK2 kinase domain.
Scaglione A, Monteonofrio L, Parisi G, Cecchetti C, Siepi F, Rinaldo C, Giorgi A, Verzili D, Zamparelli C, Savino C, Soddu S, Vallone B, Montemiglio LC. Effects of Y361-auto-phosphorylation on structural plasticity of the HIPK2 kinase domain. Protein Sci. 2018, 27(3):725-737. doi: 10.1002/pro.3367.
Open Access at Publisher