Structure and regulation of the mouse ing1 gene - Three alternative transcripts encode two PHD finger proteins that have opposite effects on p53 function

The human ING1 gene encodes nuclear protein p33(,)(ING1) CII previously sho wn to cooperate with p53 in cell growth control (Garkavtsev, I., Grigorian, I. A., Ossovskaya, V. S., Chernov, M. V., Chumakov, P, M., and Gudkov, A. V, (1998) Nature 391, 295-298), p33(ING1) belongs to a small family of prot eins from human, mouse, and yeast of approximately the same size that show significant similarity to one another within the C-terminaI PHD finger doma in and also contain an additional N-terminal region with subtle but reliabl y detectable sequence conservation Mouse ing1 is transcribed from three dif ferently regulated promoters localized within a 4-kilobase pair region of g enomic DNA The resulting transcripts share a long common region encoded by a common exon and differ in their 5'-exon sequences. Two transcripts are tr anslated into the same protein of 185 amino acids, the mouse equivalent of the human p33(ING1), while the third transcript encodes a longer protein th at has 94 additional N-terminal amino acids. Overexpression of the longer p rotein interferes with the accumulation of p53 protein and activation of p5 3-responsive promoters after DNA damage. Between the two products of ing1, only the longer one forms a complex with p53 detectable by immunoprecipitat ion, These results indicate that a single gene, ing1, encodes both p53-supp ressing and p53-activating proteins that are regulated by alternative promo ters.