ADP ribosylation factor like 2 (Arl2) protein influences microtubule dynamics in breast cancer cells.
ADP ribosylation factor like 2 (Arl2) protein is involved in the folding of tubulin peptides. Variants of the human adenocarcinoma line MCF7 cells with increased or reduced content of Arl2 protein were produced and characterized. Western blot analysis performed after separation of the different fractions of tubulins showed that the content in polymerizable soluble heterodimers was significantly increased in cells with the highest Arl2 expression level (MA+) and reduced in cells with the lowest Arl2 expression level (MA-) in comparison to control cells (MP). Microtubule dynamic instability, measured after microinjection of rhodamine-labelled tubulin in living cells, was significantly enhanced in MA+ cells and reduced in MA- cells. These alterations involved modifications of the microtubule growth and shortening rates, duration of attenuation phases, percentage of time spent in each phase (growth, shortening and attenuation) and catastrophe frequency. We also observed modifications in the expression level of the tumor suppressor protein phosphatase 2Ac, which has been shown to form a complex with Arl2. Finally, cell cycle progression was modified in these cells, particularly in regard to duration of telophase. In summary, alterations in Arl2 protein content were found to be associated with modifications in tubulin pools, microtubule dynamics as well as cell cycle progression.
Beghin
Anne
A
Laboratoire de Cytologie Analytique, UMR INSERM 590; Université de Lyon FR69008, Lyon, France. anne.beghin@recherche.univ-lyon1.fr
Honore
Stephane
S
Messana
Celine
C
Matera
Eva-Laure
EL
Aim
Jennifer
J
Burlinchon
Sandrine
S
Braguer
Diane
D
Dumontet
Charles
C
D000230:Adenocarcinoma / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D048749:Cytokinesis; D019281:Dimerization; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D008958:Models, Molecular; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D017510:Protein Folding; D054648:Protein Phosphatase 2; D034741:RNA, Small Interfering / Q000494:pharmacology; D012995:Solubility; D014162:Transfection; D014404:Tubulin / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C418662:TBCD protein, human; D014404:Tubulin; C517189:PPP2CA protein, human; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; C410130:ARL2 protein, human; D019204:GTP-Binding Proteins