Differential expression of Ran GTPase during HMBA-induced differentiation in murine erythroleukemia cells.
Murine erythroleukemia (MEL) cells undergo erythroid differentiation in vitro when treated with hexamethylene bisacetamide (HMBA). To identify genes involved in the commitment of MEL cells to differentiate, we screened a cDNA library constructed from HMBA-induced cells by differential hybridization and isolated GTPase Ran as a down-regulated gene. We observed that Ran was expressed in a biphasic mode. Following a decrease in mRNA level during the initial hours of induction, Ran re-expressed at 24-48 h, and gradually declined again. To investigate the role of Ran during MEL differentiation we constructed MEL transfectants capable to express or block Ran mRNA production constitutively. No effects were observed on cell growth and proliferation. Blockage of Ran, however, interfered with MEL cell differentiation resulting in a decrease of cell survival in the committed population.
Vanegas
N
N
Departamento de Biologi;a Celular y del Desarrollo, Centro de Investigaciones Biológicas (CSIC), Velázquez, 144, 28006, Madrid, Spain.
García-Sacristán
A
A
López-Fernández
L A
LA
Párraga
M
M
del Mazo
J
J
Hernández
P
P
Schvartzman
J B
JB
Krimer
D B
DB
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D016373:DNA, Antisense / Q000494:pharmacology; D015536:Down-Regulation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D066298:In Vitro Techniques; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology* / Q000473:pathology*; D051379:Mice; D010641:Phenotype; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D000081:Acetamides; D000970:Antineoplastic Agents; D016373:DNA, Antisense; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D012259:Ribonuclease, Pancreatic; D020931:ran GTP-Binding Protein; C014026:hexamethylene bisacetamide