title: Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) plays a role in cell cycle progression and cytoskeletal dynamics.
abstract: MARK4 is a serine-threonine kinase that phosphorylates MAP proteins, increasing microtubule dynamics. MARK4 differs from the other members of the MARK family for encoding two isoforms (MARK4L and MARK4S), differentially expressed in the nervous system, and for the peculiar localisation at the centrosome and the midbody. By cytofluorimetric analysis we showed that MARK4 is expressed throughout the cell cycle and preferentially activated during mitosis. Depletion of MARK4S affected the morphology and proliferation of fibroblasts and glioma cells, as the percentages of cells in S and G2/M phases were reduced and the percentage of cells in G1 was increased. In MARK4S silenced cells, centrosomes were duplicated and positioned apically to the nucleus, indicating that the centrosome cycle was altered and the cells arrested in G1 phase. Overexpression of MARK4L or MARK4S reduced the density of the microtubule network, confirming microtubules as the main target of MARK4, and revealed a novel co-localisation of MARK4 and vimentin. Taken together, our data confirm that MARK4 is a key component in the regulation of microtubule dynamics and highlight its major role in cell cycle progression, particularly at the G1/S transition. The co-localisation of vimentin and MARK4L suggests that MARK4 has a wide-ranging influence on cytoskeleton.
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20142 Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Rovina
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20142 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Fontana
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20142 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Monti
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20142 Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Novielli
authors.affiliation: Flow Cytometry Unit, IRCCS, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Panini
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20142 Milan, Italy.
authors.forename: Silvia Maria
authors.initials: SM
authors.lastname: Sirchia
authors.affiliation: Flow Cytometry Unit, IRCCS, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milan, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Erba
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20142 Milan, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Magnani
authors.affiliation: Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, via A. di Rudinì 8, 20142 Milan, Italy. Electronic address: lidia.larizza@unimi.it.
authors.forename: Lidia
authors.initials: L
authors.lastname: Larizza
mesh_terms: D059447:Cell Cycle Checkpoints; D002455:Cell Division; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C483047:MARK4 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Cell cycle; Centrosome; MARK4; Microtubules; Vimentin