G1/S transition in normal human T-lymphocytes requires the nuclear protein encoded by c-myb.
Exposure of peripheral blood mononuclear cells (PBMC) to an 18-base c-myb antisense oligomer before mitogen or antigen stimulation resulted in almost complete inhibition of c-myb messenger RNA and protein synthesis and blockade of T lymphocyte proliferation. Expression of early and late activation markers, interleukin-2 receptor and transferrin receptor, respectively, by PBMC was unaffected by antisense oligomer exposure as was the expression of c-myc messenger RNA. In contrast, histone H3 messenger RNA levels and DNA content were selectively decreased. These results suggest that c-myb protein deprivation does not perturb T lymphocyte activation or early molecular events that may prepare the cell for subsequent proliferation. Rather, it appears to specifically block cells in late G1 or early S phase of the cell cycle.
Gewirtz
A M
AM
Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140.
Anfossi
G
G
Venturelli
D
D
Valpreda
S
S
Sims
R
R
Calabretta
B
B
D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007399:Interphase; D008213:Lymphocyte Activation / Q000187:drug effects; D009841:Oligonucleotides / Q000494:pharmacology; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D020598:Proto-Oncogene Proteins c-myb; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D011990:Receptors, Transferrin / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D004247:DNA