Abstract
Protein p120 is a proliferation-related nucleolar protein, which is detectable early in the G1-phase of the cell cycle and peaks early in the S-phase. Most human malignant tumor cells contain much higher levels of protein p120 than do normal resting cells. To learn more about p120-associated proteins, a yeast two-hybrid screen was carried out using protein p120 as the bait. Five positive clones were identified from 2 million clones for further analysis. Three of them encoded portions of the same protein, which had identity to human SRP1. The recombinant p120 and HSRP1 proteins produced in Sf9 cells are assocated with each other, confirming the results of the yeast genetic assay. Protein SRP1 was originally characterized as a suppressor of RNA polymerase I mutations, and recently human SPR1 was identified as a receptor for nuclear localization sequences. In the present study, use of deletion mutations revealed that the binding of human SRP1 to p120 required the p120 nuclear localization signal (amino acids 96–119) and the C-terminus of human SPR1 (amino acids 453–491).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Azuma Y, Tabb MM, Vu L, Nomura M (1995) Isolation of a yeast protein kinase that is activated by the protein encoded by SRP1 (Srp1p) and phosphorylates Srp1p complexed with nuclear localizationsignal peptides. Proc Natl Acad Sci USA 92: 5159–5163
Busch H (1990) The final common pathway of cancer: presidential address. Cancer Res 50: 4830–4838
Busch RK, Busch H (1977) Antigenic proteins of nucleolar chromatin of Novikoff hepatoma ascites cells. Tumori 63: 347–357
Busch H, Busch RK, Chan PK, Kelsey D, Takahashi K (1982) Nucleolar antigens of human tumors. In: Busch H, Yeoman LC (eds) Methods in cancer research, vol 19, Academic Press, New York, pp 109–178
Chan PK, Frakes RL, Tan EM, Brattain MG, Smetana K, Busch H (1983) Indirect immunofluorescence studies of proliferating cell nuclear antigen in nucleoli of human tumor and normal tissues. Cancer Res 43:3370–3377
Cortes P, Ye ZS, Baltimore D (1994) RAG-1 interacts with the repeated amino acid motif of the human homologue of the yeast protein SPR1. Proc Natl Acad Sci USA 91: 7633–7637
Davis FM, Busch RK, Yeoman LC, Busch H (1978) Differences in nucleolar antigens of rat liver and Novikoff hepatoma ascites cells. Cancer Res 38: 1906–1915
de Beus E, Brockenbrough JS, Hong B, Aris JP (1994) Yeast NOP2 encodes an essential nucleolar protein with homology to a human proliferation marker. J Cell Biol 127: 1799–1813
Fields S, Song OK (1989) A novel genetic system to detect protein-protein interactions. Nature 340: 245–246
Freeman JW, Busch RK, Gyorkey F, Gyorkey P, Ross BE, Busch H (1988) Identification and characterization of a human proliferation-associated nucleolar antigen with a molecular weight of 120,000 expressed in early G1 phase. Cancer Res 48: 1244–1251
Freeman JW, McGrath P, Bondada V, Selliah N, Ownby H, Maloney T, Busch RK, Busch H (1991) Prognostic significance of proliferation associated nucleolar antigen p120 in human breast carcinoma. Cancer Res 51: 1973–1978
Gorlich D, Mattaj LW (1996) Nucleocytoplasmic transport. Science 271: 1513–1518
Gorlich D, Vogel F, Mills AD, Hartmann E, Laskey RA (1995) Distinct functions for the two importin subunits in nuclear protein import. Nature 377: 246–248
Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ (1993) The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75: 805–816
Lamond A, Carmo-Fonseca M (1993) The coiled body. Trends Cell Biol 3: 198–204
Loeb JDJ, Schlenstedt G, Pellman D, Kornitzer D, Silver PA, Fink GR (1995) The yeast nuclear import receptor is required for mitosis. Proc Natl Acad Sci USA 92: 7647–7651
Ochs RL, Reilly MT, Freeman JW, Busch H (1988) Intranucleolar localization of human proliferating cell nucleolar antigen p120. Cancer Res 48: 6523–6529
Perlaky L, Valdez B, Busch RK, Larson Jhiang SM, Zhang WW, Brattain M, Busch H (1992) Increased growth of NIH3T3 cells by transfection with human p120 complementary DNA and inhibition by a p120 antisence construct. Cancer Res 52: 428–436
Pollard VW, Michael WM, Nakielny S, Siomi MC, Wang F, Dreyfuss G (1996) A novel receptor-mediated nuclear protein import pathway. Cell 86: 985–994
Ren Y, Busch R, Durban E, Taylor C, Gustafson W, Valdez B, Li YP, Smetana K, Busch R (1996) Overexpression of human nucleolar proteins in insect cells: characterization of nucleolar protein p120. Protein Expr Purif 7: 212–219
Rubinfeld B, Souza B, Albert I, Muller O, Chamberlain SH, Masiarz F, Munemitsu S, Polakis P (1993) Association of the APC gene product with beta-catenin. Science 262: 1731–1734
Su LK, Vogelstein B, Kinzler K (1993) Association of the APC tumor suppressor protein with catenins. Science 262: 1734–1737
Torok I, Strand D, Schmitt R, Tick G, Torok T, Kiss I, Mechler BM (1995) The overgrown hematopoietic organs-31 tumor suppressor gene of Drosophila encodes an imortin-like protein accumulating in the nucleus at the onset of mitosis. J Cell Biol 129: 1473–1489
Valdez B, Perlaky L, Henning D, Saijo Y, Chan PK, Busch H (1994) Identification of the nuclear and nucleolar localization signals of the protein p120. J Biol Chem 269: 23776–23783
Weis K, Mattaj LW, Lamond AI (1995) Identification of hSRP1a as a functional receptor for nuclear localization sequences. Science 268: 1049–1053
Weis K, Ryder U, Lammond AI (1996) The conserved amino terminal domain of hSRP1 α is essential for nuclear protein import. EMBO J 15: 1801–1809
Yano R, Oakes M, Yamaghishi M, Dodd JA, Nomura M (1992) Cloning and characterization of SRP1, a suppressor of temperature-sensitive RNA polymerase 1 mutations inSaccharomyces cerevisiae. Mol Cell Biol 12: 5640–5651
Yano R, Oakes M, Tabb MM, Nomura M (1994) Yeast Srp1p has homology to armadillo/plakoglobin/b-catenin and participates in apparently multiple nuclear functions including the maintainance of the nuclear structure. Proc Natl Acad Sci USA 91: 6880–6884
Author information
Authors and Affiliations
Additional information
Edited by: S. A. Gerbi
Rights and permissions
About this article
Cite this article
Ren, Y., Busch, H. Human proliferation-related protein p120 interacts with HSRP1. Chromosoma 105, 553–559 (1997). https://doi.org/10.1007/BF02510492
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02510492