Abstract
The human ING1 gene encodes nuclear protein p33(ING1), previously shown 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 proteins from human, mouse, and yeast of approximately the same size that show significant similarity to one another within the C-terminal PHD finger domain and also contain an additional N-terminal region with subtle but reliably detectable sequence conservation. Mouse ing1 is transcribed from three differently regulated promoters localized within a 4-kilobase pair region of genomic DNA. The resulting transcripts share a long common region encoded by a common exon and differ in their 5'-exon sequences. Two transcripts are translated into the same protein of 185 amino acids, the mouse equivalent of the human p33(ING1), while the third transcript encodes a longer protein that has 94 additional N-terminal amino acids. Overexpression of the longer protein interferes with the accumulation of p53 protein and activation of p53-responsive promoters after DNA damage. Between the two products of ing1, only the longer one forms a complex with p53 detectable by immunoprecipitation. These results indicate that a single gene, ing1, encodes both p53-suppressing and p53-activating proteins that are regulated by alternative promoters.
Highlights
The human ING1 gene encodes nuclear protein p33ING1, previously shown to cooperate with p53 in cell growth control
Multiple Transcripts of the Mouse ing1 Gene Differ in Their 5Ј-End Sequences—In order to isolate the mouse ortholog of the ING1 gene, we screened a cDNA library prepared from senescent mouse embryonic fibroblasts, using human ING1 as a probe
The clones were identical to each other and highly similar to human ING1 through most of their length, except for the 5Ј-ends, which were different and not homologous to the human gene (Fig. 1A). This observation could be an indication of alternative splicing of mouse ing1; it could be potentially explained by cloning artifacts that occurred during the cDNA library preparation
Summary
The human ING1 gene encodes nuclear protein p33ING1, previously shown to cooperate with p53 in cell growth control Between the two products of ing, only the longer one forms a complex with p53 detectable by immunoprecipitation These results indicate that a single gene, ing, encodes both p53suppressing and p53-activating proteins that are regulated by alternative promoters. Activation of transcription from the p21/WAF1 promoter, a key mechanism of p53-mediated growth control, depends on the expression of ING1. A physical association between p33ING1 and p53 proteins is detected by immunoprecipitation These results indicated that p33ING1 is a component of the p53 signaling pathway and that p33ING1 cooperates with p53 in negative regulation of cell proliferation by modulating p53-dependent transcriptional activation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
