Effects of SET and SET-CAN on the differentiation of the human promonocytic cell line U937.
Human SET encodes a nuclear phosphoprotein with a highly acidic carboxyl-terminus, forming a SET-CAN fusion gene in a patient with acute undifferentiated leukemia. SET is highly conserved between species and is ubiquitously expressed, suggesting a widespread biological role. Even though SET is involved in chromatin remodeling and transcriptional activation, its precise role in hematopoietic cells and the contribution of SET-CAN to leukemogenesis remains unknown. We determined the effect of tetracycline-regulatable expression of SET, a deletion mutant of SET, and SET-CAN on the human promonocytic cell line U937T. The expression of SET and SET-CAN inhibited proliferation of these cells. SET accomplishes this through the induction of the differentiation program, an effect that depends on the presence of its acidic domain. SET-CAN most likely inhibits growth by interfering with hCRM1, but it also partially blocks differentiation. Our results are the first demonstration of a potential role of SET in hematopoietic differentiation.
Kandilci
A
A
Department of Genetics, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Mientjes
E
E
Grosveld
G
G
D002454:Cell Differentiation; D002455:Cell Division; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D006801:Humans; D028884:Karyopherins; D009000:Monocytes / Q000166:cytology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear; D017384:Sequence Deletion; D014157:Transcription Factors; D014162:Transfection; D020298:U937 Cells; D000097606:Exportin 1 Protein
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D028884:Karyopherins; D015514:Oncogene Proteins, Fusion; D010750:Phosphoproteins; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C513473:SET protein, human; C481746:SET-CAN fusion protein, human