Premium
Translocation of ornithine decarboxylase to the surface membrane during cell activation and transformation
Author(s) -
Heiskala Marja,
Zhang Jian,
Hayashi Shinichi,
Hölttä Erkki,
Andersson Leif C.
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.5.1214
Subject(s) - biology , ornithine decarboxylase , chromosomal translocation , transformation (genetics) , ornithine decarboxylase antizyme , cell membrane , microbiology and biotechnology , cell , biochemistry , membrane , biophysics , enzyme , gene
Ornithine decarboxylase (ODC) is highly up‐regulated in proliferating and transforming cells. Here we show that upon induction, an initial cytosolic increase of ODC is followed by translocation of a fraction of the enzyme to the surface membrane. ODC membrane translocation is mediated by a p47 phox membrane‐targeting motif‐related sequence, as indicated by reduced ODC activity in the membrane fraction of cells treated with a competing, ODC‐derived (amino acids 165–172) peptide, RLSVKFGA, which is homologous to the p47 phox membrane‐targeting sequence. p47 phox membrane translocation is known to be dependent on the phosphorylation of the targeting motif. Analogously, overexpressed ODC.S167A, a mutant ODC lacking the putative phosphorylation site Ser67, is unable to move to the surface membrane. Cells blocked with the RLSVKFGA peptide showed defective transformation, indicating that the motif‐mediated translocation of ODC is prerequisite to its biological function. Constitutive targeting of ODC to the membrane using a plasmid encoding the chimeric protein, wild‐type ODC with C‐terminal linkage to the farnesylation motif of K‐ras, caused impaired cytokinesis with an accumulation of polykaryotic cells. Impaired cytokinesis confirms that ODC is involved in mitotic cytoskeletal rearrangement events and pinpoints the importance of relevant membrane targeting to its physiological function.