Structure of pp32, an acidic nuclear protein which inhibits oncogene-induced formation of transformed foci

pp32 is a nuclear protein found highly expressed in normal tissues in those cells capable of self-renewal and in neoplastic cells. We report the cloning of cDNAs encoding human and murine pp32. The clones encode a 28.6-kDa protein; approximately two-thirds of the N-terminal predicts an amphipathic a...

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Bibliographic Details
Published in:Molecular biology of the cell 1996-12, Vol.7 (12), p.2045-2056
Main Authors: Chen, T H, Brody, J R, Romantsev, F E, Yu, J G, Kayler, A E, Voneiff, E, Kuhajda, F P, Pasternack, G R
Format: Article
Language:English
Subjects:
3T3 Cells
Amino Acid Sequence
Animals
Base Sequence
Cell Line
DNA, Complementary
Gene Expression
Gene Expression Regulation
Genes, myc
Genes, ras
Humans
Mice
Molecular Sequence Data
Nuclear Proteins - chemistry
Nuclear Proteins - genetics
Oncogenes
Phosphoproteins - chemistry
Phosphoproteins - genetics
Rats
RNA, Messenger
Transcription, Genetic
Transformation, Genetic
Tumor Cells, Cultured
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Summary:pp32 is a nuclear protein found highly expressed in normal tissues in those cells capable of self-renewal and in neoplastic cells. We report the cloning of cDNAs encoding human and murine pp32. The clones encode a 28.6-kDa protein; approximately two-thirds of the N-terminal predicts an amphipathic alpha helix containing two possible nuclear localization signals and a potential leucine zipper motif. The C-terminal third is exceptionally acidic, comprised of approximately 70% aspartic and glutamic acid residues; the predicted pI of human pp32 is 3.81. Human and murine pp32 cDNAs are 88% identical; the predicted proteins are 89% identical and 95% similar. Although the structure of pp32 is suggestive of a transcription factor, pp32 did not significantly modulate transcription of a reporter construct when fused to the Gal4 DNA-binding domain. In contrast, in cotransfection experiments, pp32 inhibited the ability of a broad assortment of oncogene pairs to transform rat embryo fibroblasts, including ras + myc, ras + jun, ras + E1a, ras + mutant p53, and E6 + E7. In related experiments, pp32 inhibited the ability of Rat 1a-myc cells to grow in soft agar, whereas it failed to affect ras-induced focus formation in NIH3T3 cells. These results suggest that pp32 may play a key role in self-renewing cell populations where it may act in the nucleus to limit their sensitivity to transformation.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.7.12.2045