Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells.
During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ipl)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3-dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-ras(G12V)), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-1(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes.
Department of Hematology/Oncology, Osaka University Medical School, Osaka 565-0871, Japan.
A
A
Kawasaki
I
I
Matsumura
Miyagawa Ji
S
S
Ezoe
H
H
Tanaka
Y
Y
Terada
M
M
Tatsuka
T
T
Machii
H
H
Miyazaki
Y
Y
Furukawa
Y
Y
Kanakura
D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001854:Bone Marrow Cells / Q000166:cytology; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication; D004920:Erythropoiesis / Q000502:physiology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D011905:Genes, ras; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010703:Phorbol Esters / Q000494:pharmacology; D011123:Polyploidy; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D013926:Thrombopoietin / Q000494:pharmacology; D014158:Transcription, Genetic
D007377:Interleukin-3; D010703:Phorbol Esters; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D013926:Thrombopoietin; D011494:Protein Kinases; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases