New type of interaction between the SARAH domain of the tumour suppressor RASSF1A and its mitotic kinase Aurora A.

ABSTRACT: The tumour suppressor protein RASSF1A is phosphorylated by Aurora A kinase, thereby impairing its tumour suppressor function. Consequently, inhibiting the interaction between Aurora A and RASSF1A may be used for anti-tumour therapy. We used recombinant variants of RASSF1A to map the sites of interaction with Aurora A. The phosphorylation kinetics of three truncated RASSF1A variants has been analysed. Compared to the RASSF1A form lacking the 120 residue long N-terminal part, the K_m value of the phosphorylation is increased from 10 to 45 μM upon additional deletion of the C-terminal SARAH domain. On the other hand, deletion of the flexible loop (Δ177-197) that precedes the phosphorylation site/s (T202/S203) results in a reduction of the k_cat value from about 40 to 7 min

SUBMITTER: Szimler T 

PROVIDER: S-EPMC6447619 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature