p27KIP1 and GATA-1 are potential downstream molecules in activin A-induced differentiation and apoptosis pathways in CML cells.
p27KIP1 is known as a regulator of cellular differentiation and apoptosis in human cancer cells. We have previously reported that human chronic myeloid leukemia (CML) KU812 and K562 cells show inhibited cellular proliferation in response to treatment with activin A, a member of TGF-beta superfamily. Apoptosis and erythroid differentiation can be induced in KU812 and K562 cells, respectively. We report herein that activin A induced the expression of p27KIP1 in CML cells along with the induction of cellular differentiation and apoptosis. There are putative binding sequences of erythroid-related transcription factor GATA-1 in the promoter region of the human p27KIP1 gene. Expression of GATA-1 protein in activin A-treated KU812 and K562 cells showed dissimilar regulation in these two cell lines. Induction of p27KIP1 was commonly observed, but it did not correspond to the expression levels of GATA-1 in either line of activin A-treated CML cells. In addition, ERK protein was rapidly and transiently activated with activin A in both types of CML cells, suggesting that phosphorylation of ERK is required for activin A signaling in CML cells. These results indicate that both p27KIP1 induction and regulation of GATA-1 play essential roles in activin A-induced erythroid differentiation and apoptosis.
Fukuchi
Yumi
Y
Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Tokyo 160-8582, Japan.
Yamato
Kenji
K
Kawamura
Chiharu
C
Ikeda
Yasuo
Y
Kizaki
Masahiro
M
D028341:Activins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050982:GATA1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D018797:Cell Cycle Proteins; D050982:GATA1 Transcription Factor; D028341:Activins; D050760:Cyclin-Dependent Kinase Inhibitor p27