Deregulation of translational control of the 65-kDa regulatory subunit (PR65 alpha) of protein phosphatase 2A leads to multinucleated cells.
Efficient translation of the mRNA encoding the 65-kDa regulatory subunit (PR65 alpha) of protein phosphatase 2A (PP2A) is prevented by an out of frame upstream AUG and a stable stem-loop structure (delta G = -55.9 kcal/mol) in the 5'-untranslated region (5'-UTR). Deletion of the 5'-UTR allows efficient translation of the PR65 alpha message in vitro and overexpression in COS-1 cells. Insertion of the 5'-UTR into the beta-galactosidase leader sequence dramatically inhibits translation of the beta-galactosidase message in vitro and in vivo, confirming that this sequence functions as a potent translation regulatory sequence. Cells transfected or microinjected with a PR65 alpha expression vector lacking the 5'-UTR, express high levels of PR65 alpha, accumulating in both nucleus and cytoplasm. PR65 alpha overexpressing rat embryo fibroblasts (REF-52 cells) become multinucleated. These data and previous results (Mayer-Jaekel, R. E., Ohkura, H., Gomes, R., Sunkel, C. E., Baumgartner, S., Hemmings, B. A., and Glover, D. M. (1993) Cell 72, 621-633) suggest that PP2A participates in the regulation of both mitosis and cytokinesis.
Wera
S
S
Friedrich Miescher-Institut, Basel, Switzerland.
Fernandez
A
A
Lamb
N J
NJ
Turowski
P
P
Hemmings-Mieszczak
M
M
Mayer-Jaekel
R E
RE
Hemmings
B A
BA
D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics*; D002460:Cell Line; D003062:Codon; D017931:DNA Primers; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D054648:Protein Phosphatase 2; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017384:Sequence Deletion
D003062:Codon; D017931:DNA Primers; D012333:RNA, Messenger; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2