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Cell Growth & Differentiation, Vol 1, Issue 1 17-25, Copyright © 1990 by American Association of Cancer Research


ARTICLES

Deletion of a splice donor site ablates expression of the following exon and produces an unphosphorylated RB protein unable to bind SV40 T antigen

JY Shew, PL Chen, R Bookstein, EY Lee and WH Lee
Department of Pathology, University of California, San Diego, La Jolla 92093.

Studies of mutated retinoblastoma (RB) proteins in human tumor cells potentially reveal regions of the normal RB gene product that are required for its cancer suppression function. We here characterize a mutated RB protein of Mr 104,000 (p104) from a primary small-cell lung carcinoma. Unlike normal RB protein (pp110RB), p104 was unphosphorylated and unable to bind T antigen of SV40 both in vivo and in vitro. On the other hand, nuclear localization and DNA binding activity were preserved in the mutated protein. p104 was immunoprecipitable with four separate polyclonal antibodies recognizing different epitopes of the RB polypeptide, suggesting the presence of most exons in their correct reading frame. Following reverse transcription and in vitro amplification, RB mRNA from this tumor was shown to lack nucleotides encoded by exon 16. Analysis of genomic DNA from this tumor showed that exon 16 and its flanking splice donor and acceptor sequences were present and entirely normal; however, a 43-base pair (bp) region containing the splice donor site of intron 15 was deleted instead. Exon 15 was joined directly to exon 17 during mRNA processing via a cryptic splice donor site; exon 16 was presumably skipped because the preceding mutated intron was of insufficient length (less than 80 bp) for normal RB mRNA processing. These results demonstrate that loss of a single small exon disrupts several important biochemical properties of RB protein. In addition, sequence features of the 43-bp depletion suggest involvement of a novel deletional mechanism.


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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1990 by the American Association of Cancer Research.