THE HUMAN PROTEIN P19(ARF) IS NOT DETECTED IN HEMATOPOIETIC HUMAN CELL-LINES THAT ABUNDANTLY EXPRESS THE ALTERNATIVE BETA-TRANSCRIPT OF THEP16(INK4A) MTS1 GENE/

The p16/MTS1/CDKN2 gene on human chromosome band 9p21 encodes two unre lated proteins: p16(INK4a), a inhibitor of the cyclin D-dependent kina ses and CDK6, and the structurally unrelated p19(ARF) protein that arr ests cell growth in G(1)/S and also in G(2)/M. By use of polyclonal an tibodies, the human p19(ARF) (hp19(ARF)) protein has been identified i n 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 p19(ARF) accumulated in presenescent or senescent cell s. Interestingly, hp19(ARF) was not detected in several hemopoietic tu mor cell lines (mainly of B-type lymphoid origin) that expressed abund ant amounts of the p16 beta transcript. This finding indicates that in certain tumors, the expression of hp19(ARF) RNA and protein may be un coupled, Furthermore, it suggests that disruption of a translational m echanism may be involved in the inactivation of hp19(ARF).