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Expression of the p16 and p15 Cyclin-dependent Kinase Inhibitors in Lymphocyte Activation and Neuronal Differentiation¹

The Sam and Rose Stein Institute for Research on Aging and Department of Medicine, University of California, San Diego, La Jolla, California 92093-0663

The cyclin-dependent kinase inhibitors p16^INK4/MTS1 and p15^INK4B/MTS2 have been mapped to a region in chromosome 9 (p21) that is deleted frequently in acute lymphoblastic leukemias and malignant gliomas. To gain insight into the functions of these inhibitors in lymphocytes and neuronal cells, we studied the expression of p15 and p16 during lymphocyte mitogenesis and neuronal differentiation. Expression of p15 was extinguished during lymphocyte activation, concomitant with an increase in retinoblastoma kinase activity. The differentiation of the embryonic teratocarcinoma cell line NT2 into postmitotic neurons (hNT) was associated with enhanced expression of p15 and p16 proteins. These findings suggest that p15 and p16 play a role in maintaining cell quiescence in lymphocytes and neuronal cells, respectively. Deletions of these genes may thus promote unrestrained growth.

¹ This paper was supported in part by NIH Grant CA64976, by Grant 3RT-c0075 from the University of California Tobacco Research Program, and by a grant from the CIBA-GEIGY Corporation.

² To whom requests for reprints should be addressed, at Department of Medicine, University of California, 9500 Gilman Drive, La Jolla, CA 92093-0663.

Received 6/12/95. Accepted 8/ 4/95.

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