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The PML gene encodes a phosphoprotein associated with the nuclear matrix
KS Chang, YH Fan, M Andreeff, J Liu and ZM Mu
Department of Hematology, University of Texas M.D. Anderson Cancer Center,
Houston 77030, USA.
The t(15;17)(q22;q12) translocation is the cytogenetic hallmark of acute
promyelocytic leukemia (APL). The PML and retinoic acid receptor- alpha
(RAR alpha) transcription factor genes are involved at translocation
breakpoint. To elucidate the biologic function of PML, antipeptide antibody
against PML protein was raised in rabbits. This antibody was able to detect
a 90-kD PML protein and a 110-kD PML-RAR alpha fusion protein by Western
blotting and a nuclear speckled pattern in all cell lines by
immunofluorescent staining. In K562 and NIH/3T3 cells transfected with a
PML expression plasmid, we found PML to be associated with the nuclear
matrix. Our results also showed that PML is a phosphorprotein. A weak
signal was detected in a Western blot containing the immunoprecipitated PML
protein using the phosphotyrosine- specific monoclonal antibody. Therefore,
at least one of the sites was phosphorylated by a tyrosine kinase. From our
analysis of the phosphoamino acids of the PML protein by complete
hydrolysis and thin- layer chromatography, we concluded that both tyrosine
and serine residues of PML are phosphorylated. To investigate whether
expression of the PML protein is cell-cycle related, HeLa cells
synchronized at various phases of the cell cycle were analyzed by
immunofluorescence staining and confocal microscopy for PML expression. We
found that PML was expressed at a lower level in S, G2, and M phases and at
a significantly higher level in G1 phase. Our study showed that PML has
many similar properties compared with the tumor suppressor, eg, Rb. These
findings further support the important role of PML in APL pathogenesis.
Volume 85,
Issue 12,
pp. 3646-3653,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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