Profilin 1 is a crucial actin regulator, interacting with monomeric actin and several actin-binding proteins controlling actin polymerization. Recently, it has become evident that this profilin isoform associates with microtubules via formins and interferes with microtubule elongation at the cell periphery. Recruitment of microtubule-associated profilin upon extensive actin polymerizations, for example, at the cell edge, enhances microtubule growth, indicating that profilin contributes to the coordination of actin and microtubule organization. Here, we provide further evidence for the profilin-microtubule connection by demonstrating that it also functions in centrosomes where it impacts on microtubule nucleation.

• MeSH
• aktiny metabolismus   MeSH
• Caco-2 buňky MeSH
• centrozom metabolismus   MeSH
• forminy metabolismus   MeSH
• genový knockout MeSH
• lidé MeSH
• melanom experimentální metabolismus   patologie   MeSH
• mikrofilamentové proteiny metabolismus   MeSH
• mikrotubuly metabolismus   MeSH
• myši MeSH
• nádory kůže metabolismus   patologie   MeSH
• polymerizace MeSH
• profiliny genetika   metabolismus   MeSH
• signální transdukce genetika   MeSH
• transfekce MeSH
• tubulin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Profilin controls actin nucleation and assembly processes in eukaryotic cells. Actin nucleation and elongation promoting factors (NEPFs) such as Ena/VASP, formins, and WASP-family proteins recruit profilin:actin for filament formation. Some of these are found to be microtubule associated, making actin polymerization from microtubule-associated platforms possible. Microtubules are implicated in focal adhesion turnover, cell polarity establishment, and migration, illustrating the coupling between actin and microtubule systems. Here we demonstrate that profilin is functionally linked to microtubules with formins and point to formins as major mediators of this association. To reach this conclusion, we combined different fluorescence microscopy techniques, including superresolution microscopy, with siRNA modulation of profilin expression and drug treatments to interfere with actin dynamics. Our studies show that profilin dynamically associates with microtubules and this fraction of profilin contributes to balance actin assembly during homeostatic cell growth and affects micro-tubule dynamics. Hence profilin functions as a regulator of microtubule (+)-end turnover in addition to being an actin control element.

• MeSH
• aktiny metabolismus   MeSH
• buněčná adheze MeSH
• buněčné kultury MeSH
• cytoskelet metabolismus   MeSH
• fetální proteiny metabolismus   MeSH
• fluorescenční mikroskopie MeSH
• fokální adheze metabolismus   MeSH
• HEK293 buňky MeSH
• jaderné proteiny metabolismus   MeSH
• lidé MeSH
• malá interferující RNA MeSH
• melanom experimentální MeSH
• mikrofilamenta metabolismus   MeSH
• mikrofilamentové proteiny metabolismus   MeSH
• mikrotubuly metabolismus   MeSH
• pohyb buněk fyziologie   MeSH
• profiliny metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: 9-[2-(phosphonomethoxy)ethyl] guanine (PMEG) is a nucleotide analogue with anticancer activity. Here we investigate the role of ERK, p38, JNK and AKT kinases in PMEG-induced apoptosis. MATERIALS AND METHODS: CCRF-CEM and HL-60 leukemia cells were used to assess MAPK mRNA and protein expression in PMEG-treated cells. MAPK activation was measured using phospho-specific antibodies. Apoptosis was evaluated by caspase-3 and PARP cleavage. RESULTS: Up-regulation of p38β, γ and δ mRNA were observed following PMEG treatment of CCRF-CEM cells, however, the total protein expression remained unchanged. Neither PMEG nor its analogue 9-[2-(phosphonomethoxy) ethyl]-2,6-diaminopurine (PMEDAP) induced p38 kinase phosphorylation in CCRF-CEM cells, whereas increased p38 phosphorylation was observed in HL-60 cells. The ERK pathway was also activated by these compounds. Pretreatment of the cells with the p38 inhibitor SB203580 diminished drug-induced apoptosis whereas inhibition of ERK, JNK or AKT pathways did not. [corrected]. CONCLUSION: PMEG- and PMEDAP-induced. [corrected].

• MeSH
• adenin analogy a deriváty   farmakologie   MeSH
• aktivace enzymů účinky léků   MeSH
• antitumorózní látky farmakologie   MeSH
• extracelulárním signálem regulované MAP kinasy antagonisté a inhibitory   metabolismus   MeSH
• guanin analogy a deriváty   farmakologie   MeSH
• HL-60 buňky MeSH
• kaspasa 3 metabolismus   MeSH
• lidé MeSH
• MAP kinasa-kinasa 4 antagonisté a inhibitory   metabolismus   MeSH
• MAP kinasový signální systém účinky léků   MeSH
• messenger RNA biosyntéza   genetika   MeSH
• mitogenem aktivované proteinkinasy p38 antagonisté a inhibitory   biosyntéza   genetika   metabolismus   MeSH
• mitogenem aktivované proteinkinasy antagonisté a inhibitory   biosyntéza   genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• organofosforové sloučeniny farmakologie   MeSH
• protoonkogenní proteiny c-akt antagonisté a inhibitory   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH