Down-regulation by retinoic acid of the catalytic subunit of protein phosphatase type 2A during granulocytic differentiation of HL-60 cells.
Activity of protein phosphatase measured in the absence of divalent cations was decreased by 50% during all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation into the granulocytic phenotype. Treatment of HL-60 cells with ATRA led to a dramatic decrease in the amount of protein phosphatase type 2A (PP2A) protein, whereas that of protein phosphatase type 1 (PP1) protein was relatively constant, as detected by immunoblotting with antibodies specific to PP1 and PP2A. The decreased phosphatase activity may be mainly due to a decrease in the expression of the PP2A protein. The mRNA level of PP2A beta was markedly decreased within 5 h after addition of ATRA, but there was only a slight increase in the mRNA level of PP2A alpha. Selective down-regulation of PP2A beta mRNA clearly preceded the cell differentiation induced by ATRA treatment. Thus, PP2A is down-regulated during ATRA-induced differentiation of HL-60 cells into granulocytes.
Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
I
I
Tawara
M
M
Nishikawa
K
K
Morita
K
K
Kobayashi
H
H
Toyoda
S B
SB
Omay
H
H
Shima
M
M
Nagao
T
T
Kuno
C
C
Tanaka
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D003600:Cytosol / Q000201:enzymology; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D006098:Granulocytes / Q000166:cytology* / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D046911:Macromolecular Substances; D008970:Molecular Weight; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D046911:Macromolecular Substances; D012334:RNA, Neoplasm; D014212:Tretinoin; D010749:Phosphoprotein Phosphatases; D013755:Tetradecanoylphorbol Acetate