XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Posters
30.
ChaNGES IN COfILIN PHOSPHOrYLaTION DUrING THE aPOPTOSIS of
LEUKEMIC JURL-MK1 CELLS
Dana Grebeňová, Michaela Pluskalová, Zbyněk Hrkal and Kateřina Kuželová
Institute of Hematology and Blood Transfusion, Prague, Czech Republic
Cofilin is a key mediator of actin dynamics which is involved in processes requiring changes
in the cytoskeleton structure, e. g. cell migration, cell division and adhesion to the extracellular
matrix. It promotes actin filament severing and depolymerization, facilitating the
breakdown of existing filaments and the enhancement of filament growth from newly
created barbed ends. Cofilin phosphorylation at Ser3 is known to prevent its activity.
We explored the effect of two antileukemic drugs (suberoylanilide hydroxamic acid and
imatinib mesylate) on JURL-MK1 cell adhesivity to fibronectin and on cofilin activity.
Under certain conditions, both compounds were able to enhance the cellular adhesivity
and cofilin phosphorylation (inactivation) increased as expected. To the contrary, higher
drug doses induced the apoptosis which was accompagnied by a decrease in cellular
adhesivity to fibronectin and by F-actin disassembly. Surprisingly, cofilin phosphorylation
at Ser3 markedly increased even in these conditions. This increase could be at least
partly inhibited by the apoptosis inhibitor Q-VD-OPh, but not by the inhibitor of ROCK,
one of the main regulators of cofilin activity. We speculate that some prominent actin
structures have to be protected from cofilin-mediated destruction in order to assure
the cell disintegration into apoptotic bodies. The phosphorylated (inactive) cofilin was
concentrated in small distinct spots distributed throughout the cytoplasm.
Ackowledgement: This work was supported by the grant No 301/09/1026 from the Grant
Agency of the Czech Republic.
148 XXII. Biochemistry Congress, Martin