The human protein p19ARF is not detected in hemopoietic human cell lines that abundantly express the alternative beta transcript of the p16INK4a/MTS1 gene.
The p16/MTS1/CDKN2 gene on human chromosome band 9p21 encodes two unrelated proteins: p16INK4a, a specific inhibitor of the cyclin D-dependent kinases CKD4 and CDK6, and the structurally unrelated p19ARF protein that arrests cell growth in G1/S and also in G2/M. By use of polyclonal antibodies, the human p19ARF (hp19ARF) protein has been identified in the nucleus of various cells including normal cultured fibroblasts. The level of this protein did not fluctuate throughout the cell cycle and was more elevated in fibroblasts with limited or arrested growth, suggesting that p19ARF accumulated in presenescent or senescent cells. Interestingly, hp19ARF was not detected in several hemopoietic tumor cell lines (mainly of B-type lymphoid origin) that expressed abundant amounts of the p16beta transcript. This finding indicates that in certain tumors, the expression of hp19ARF RNA and protein may be uncoupled. Furthermore, it suggests that disruption of a translational mechanism may be involved in the inactivation of hp19ARF.
Della Valle
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INSERM U-301, Institute de Génétique Moléculaire, Paris, France.
Duro
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Bernard
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Larsen
C J
CJ
D000818:Animals; D002051:Burkitt Lymphoma / Q000473:pathology; D019556:COS Cells; D016922:Cellular Senescence; D002648:Child; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000473:pathology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D014176:Protein Biosynthesis; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF
D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025803:Tumor Suppressor Protein p14ARF