Masuccio Alessia,

University / Clinic:
Institute: Biocenter CCB - Dep. Medical Biochemistry
Research Area: Cell Cycle


Research Topic:
Skp2 is an F-box protein and substrate-targeting subunit of the E3 ubiquitin ligase SCFSkp2 and it is found frequently overexpressed in different types of cancers 1.
SCFSkp2 recognizes and ubiquitinates the T187-phosphorylated form of the Cyclin-dependent kinase (Cdk) inhibitor p27Kip1 targeting it for 26S proteasome-mediated degradation2. It has been shown that statins can induce G1 cell cycle arrest in normal and cancer cells by increasing p27Kip1 levels 3,4. Interestingly, we observed that Lovastatin, via bloackade of protein geranygeranylation, induces the degradation of Skp2, which may explain p27Kip1 accumulation. This led us to hypothesize that one or more geranygeranylated proteins, whose function is perturbed by Lovastatin, may play an important role in regulating Skp2 stability. stylepit

Selected publications:
  Vosper J, Masuccio A, Kullmann M, Ploner C, Geley S, Hengst L
Statin-induced depletion of geranylgeranyl pyrophosphate inhibits cell proliferation by a novel pathway of Skp2 degradation
Oncotarget. 2015 Feb 20;6(5):2889-902