Reduced Ran expression in Ran(+/-) fibroblasts increases cytokine-stimulated nuclear abundance of the AP-1 subunits c-Fos and c-Jun.
Ran (Ras-related nuclear protein), a Ras family GTPase, is involved in multiple cellular functions, including the regulation of DNA replication, cell cycle progression, nuclear structure formation, RNA processing-exportation, and nuclear protein importation. Ran(+/-) embryonic stem (ES) cells were produced in an attempt to generate Ran null mutant mice. Even after an extremely large number of blastocyst injections, no Ran(+/-) chimeric mice could be generated. Ran(+/-) ES cell-derived fibroblasts showed reduced Ran protein expression, and manifested augmented nuclear abundance of AP-1 factors (c-Jun and c-Fos) upon cytokine stimulation. Our experiments demonstrated that intracellular Ran protein levels controlled the nuclear presence of certain transcription factors, such as c-Fos and c-Jun.
Laboratory of Immunology, Centre hospitalier de l'Université de Montréal (CRCHUM)-Hôpital Notre-Dame, Montreal, Quebec, Canada.
Diep Ngoc Thi
DN
Pham
Hongyu
H
Luo
Jiangping
J
Wu
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D021122:Protein Subunits / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism*
D050976:Basic-Leucine Zipper Transcription Factors; D016207:Cytokines; D021122:Protein Subunits; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D020931:ran GTP-Binding Protein