The transcription factor interferon regulatory factor-1 is expressed during both early G1 and the G1/S transition in the prolactin-induced lymphocyte cell cycle.
PRL induces quiescent Nb2 rat T-lymphoma cells to undergo mitogenesis. Upon PRL stimulation, the transcription factor interferon regulatory factor-1 (IRF-1) is induced as a novel T-cell activation gene in Nb2 cells. Surprisingly, IRF-1 is expressed twice during a single PRL-induced growth cycle: first during the early G1 phase, in an immediate transient peak from 15 min to 2 h, and second during the G1/S phase transition, in a broader peak beginning at 8 h. The unusual biphasic expression of IRF-1 mRNA is accompanied both times by de novo IRF-1 protein synthesis. However, the rate of IRF-1 protein turnover appears to be different in G1 and S phases. IRF-1 protein expressed in G1 exhibits a half-life of about 25 min, whereas in the S phase, the half-life is about 60 min. By washing out PRL at various times during G1, we found a direct correlation among the length of PRL exposure, the second peak of IRF-1 mRNA expression, and DNA synthesis. Our data suggest that PRL and one putative nuclear mediator, IRF-1, may be important in two distinct phases of the cell cycle: first in cell cycle activation, and then in S phase progression.
Stevens
A M
AM
Department of Microbiology, Baylor College of Medicine, Houston, Texas 77030.
Yu-Lee
L Y
LY
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D050856:Interferon Regulatory Factor-1; D007399:Interphase / Q000187:drug effects*; D016399:Lymphoma, T-Cell; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D016196:S Phase / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494259:Irf1 protein, rat; D010750:Phosphoproteins; D014157:Transcription Factors; D011388:Prolactin