LYAR, A NOVEL NUCLEOLAR PROTEIN WITH ZINC-FINGER DNA-BINDING MOTIFS, IS INVOLVED IN CELL-GROWTH REGULATION

A cDNA encoding a novel zinc finger protein has been isolated from a m ouse T-cell leukemia line on the basis of its expression of a Ly-1 epi tope in a lambdagt11 library. The putative gene was mapped on mouse ch romosome 1, closely linked to Idh-1, but not linked to the Ly-1 (CD5) gene. The cDNA is therefore named Ly-1 antibody reactive clone (LYAR). The putative polypeptide encoded by the cDNA consists of 388 amino ac ids with a zinc finger motif and three copies of nuclear localization signals. Antibodies raised against a LYAR fusion protein reacted with a protein of 45 kD on Western blots and by immunoprecipitation. Immuno localization indicated that LYAR was present predominantly in the nucl eoli. The LYAR mRNA was not detected in brain, thymus, bone marrow, li ver, heart, and muscle. Low levels of LYAR mRNA were detected in kidne y and spleen. However, the LYAR gene was expressed at very high levels in immature spermatocytes in testis. The LYAR mRNA is present at high levels in early embryos and preferentially in fetal liver and fetal t hymus. A number of B- and T-cell leukemic lines expressed LYAR at high levels, although it was not detectable in bone marrow and thymus. Dur ing radiation-induced T-cell leukemogenesis, high levels of LYAR were expressed in preleukemic thymocytes and in acute T leukemia cells. Fib roblast cells overexpressing the LYAR cDNA from a retrovirus vector, t hough not phenotypically transformed in vitro, had increased ability t o form tumors in nu/nu mice. Therefore, LYAR may function as a novel n ucleolar oncoprotein to regulate cell growth.