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. 1989 Nov 1;109(5):1937–1946. doi: 10.1083/jcb.109.5.1937

Loss of proliferative potential during terminal differentiation coincides with the decreased abundance of a subset of heterogeneous ribonuclear proteins

PMCID: PMC2115836  PMID: 2808514

Abstract

The decrease in abundance of a subset of highly conserved basic nuclear proteins is established to correlate with the loss of proliferative potential in association with the process of terminal differentiation in murine mesenchymal stem cells and human keratinocytes. These proteins, designated P2Ps for proliferation potential proteins, have apparent molecular masses of 30-40 kD, are associated with the 30-40S substructures of nuclear hnRNP complexes, and are recognized by antibodies made against core proteins of hnRNP particles. They also share an epitope in common with heat shock protein-90 (hsp90) and are recognized by two mAbs against hsp90. Two-dimensional electrophoretic Western blots furthermore show that P2Ps make up a subset of hnRNP proteins. Cells that possess these proteins express the potential to proliferate whether or not they are traversing the cell cycle. These include rapidly growing cells, reversibly growth-arrested cells, and nonterminally differentiated cells. In contrast, cells that have irreversibly lost their proliferative potential, such as terminally differentiated cells, show a marked reduction in the abundance of P2Ps as determined by immunodetection on Western blots. A correlation, therefore, exists between the presence of this subset of nuclear proteins and the proliferative potential in two cell types. These results raise the possibility that as a subset of hnRNP proteins, P2Ps may mediate posttranscriptional control of the processing of specific RNAs required for cell proliferation.

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Selected References

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  1. Almendral J. M., Huebsch D., Blundell P. A., Macdonald-Bravo H., Bravo R. Cloning and sequence of the human nuclear protein cyclin: homology with DNA-binding proteins. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1575–1579. doi: 10.1073/pnas.84.6.1575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Choi Y. D., Grabowski P. J., Sharp P. A., Dreyfuss G. Heterogeneous nuclear ribonucleoproteins: role in RNA splicing. Science. 1986 Mar 28;231(4745):1534–1539. doi: 10.1126/science.3952495. [DOI] [PubMed] [Google Scholar]
  3. Diamond L., O'Brien T. G., Rovera G. Inhibition of adipose conversion of 3T3 fibroblasts by tumour promoters. Nature. 1977 Sep 15;269(5625):247–249. doi: 10.1038/269247a0. [DOI] [PubMed] [Google Scholar]
  4. Dreyfuss G., Swanson M. S., Piñol-Roma S. Heterogeneous nuclear ribonucleoprotein particles and the pathway of mRNA formation. Trends Biochem Sci. 1988 Mar;13(3):86–91. doi: 10.1016/0968-0004(88)90046-1. [DOI] [PubMed] [Google Scholar]
  5. Elder P. K., Schmidt L. J., Ono T., Getz M. J. Specific stimulation of actin gene transcription by epidermal growth factor and cycloheximide. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7476–7480. doi: 10.1073/pnas.81.23.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fakan S., Leser G., Martin T. E. Immunoelectron microscope visualization of nuclear ribonucleoprotein antigens within spread transcription complexes. J Cell Biol. 1986 Oct;103(4):1153–1157. doi: 10.1083/jcb.103.4.1153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Krawisz B. R., Scott R. E. Coupling of proadipocyte growth arrest and differentiation. I. Induction by heparinized medium containing human plasma. J Cell Biol. 1982 Aug;94(2):394–399. doi: 10.1083/jcb.94.2.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  9. LeStourgeon W. M., Beyer A. L., Christensen M. E., Walker B. W., Poupore S. M., Daniels L. P. The packaging proteins of core hnRNP particles and the maintenance of proliferative cell states. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):885–898. doi: 10.1101/sqb.1978.042.01.090. [DOI] [PubMed] [Google Scholar]
  10. Leser G. P., Escara-Wilke J., Martin T. E. Monoclonal antibodies to heterogeneous nuclear RNA-protein complexes. The core proteins comprise a conserved group of related polypeptides. J Biol Chem. 1984 Feb 10;259(3):1827–1833. [PubMed] [Google Scholar]
  11. Leser G. P., Martin T. E. Changes in heterogeneous nuclear RNP core polypeptide complements during the cell cycle. J Cell Biol. 1987 Nov;105(5):2083–2094. doi: 10.1083/jcb.105.5.2083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Linzer D. I., Nathans D. Growth-related changes in specific mRNAs of cultured mouse cells. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4271–4275. doi: 10.1073/pnas.80.14.4271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Martin T. E., McCarthy B. J. Synthesis and turnover of RNA in the 30-S nuclear ribonucleoprotein complexes of mouse ascites cells. Biochim Biophys Acta. 1972 Aug 25;277(2):354–367. doi: 10.1016/0005-2787(72)90417-0. [DOI] [PubMed] [Google Scholar]
  14. Martin T., Billings P., Pullman J., Stevens B., Kinniburgh A. Substructure of nuclear ribonucleoprotein complexes. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):899–909. doi: 10.1101/sqb.1978.042.01.091. [DOI] [PubMed] [Google Scholar]
  15. O'Farrell P. Z., Goodman H. M., O'Farrell P. H. High resolution two-dimensional electrophoresis of basic as well as acidic proteins. Cell. 1977 Dec;12(4):1133–1141. doi: 10.1016/0092-8674(77)90176-3. [DOI] [PubMed] [Google Scholar]
  16. Osheim Y. N., Miller O. L., Jr, Beyer A. L. RNP particles at splice junction sequences on Drosophila chorion transcripts. Cell. 1985 Nov;43(1):143–151. doi: 10.1016/0092-8674(85)90019-4. [DOI] [PubMed] [Google Scholar]
  17. Santarén J. F., Bravo R. A basic cytoplasmic protein (p27) induced by serum in growth-arrested 3T3 cells but constitutively expressed in primary fibroblasts. EMBO J. 1986 May;5(5):877–882. doi: 10.1002/j.1460-2075.1986.tb04298.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Scott R. E., Estervig D. N., Tzen C. Y., Minoo P., Maercklein P. B., Hoerl B. J. Nonterminal differentiation represses the neoplastic phenotype in spontaneously and simian virus 40-transformed cells. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1652–1656. doi: 10.1073/pnas.86.5.1652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Scott R. E., Florine D. L., Wille J. J., Jr, Yun K. Coupling of growth arrest and differentiation at a distinct state in the G1 phase of the cell cycle: GD. Proc Natl Acad Sci U S A. 1982 Feb;79(3):845–849. doi: 10.1073/pnas.79.3.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Scott R. E., Hoerl B. J., Wille J. J., Jr, Florine D. L., Krawisz B. R., Yun K. Coupling of proadipocyte growth arrest and differentiation. II. A cell cycle model for the physiological control of cell proliferation. J Cell Biol. 1982 Aug;94(2):400–405. doi: 10.1083/jcb.94.2.400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Scott R. E., Wilke M. S., Wille J. J., Jr, Pittelkow M. R., Hsu B. M., Kasperbauer J. L. Human squamous carcinoma cells express complex defects in the control of proliferation and differentiation. Am J Pathol. 1988 Nov;133(2):374–380. [PMC free article] [PubMed] [Google Scholar]
  22. Sidhu R. S. Two-dimensional electrophoretic analyses of proteins synthesized during differentiation of 3T3-L1 preadipocytes. J Biol Chem. 1979 Nov 10;254(21):11111–11118. [PubMed] [Google Scholar]
  23. Spelsberg T. C., Knowler J. T., Moses H. L. Specific methods for the isolation of nuclei from chick oviduct. Methods Enzymol. 1974;31:263–279. doi: 10.1016/0076-6879(74)31028-2. [DOI] [PubMed] [Google Scholar]
  24. Spiegelman B. M., Green H. Control of specific protein biosynthesis during the adipose conversion of 3T3 cells. J Biol Chem. 1980 Sep 25;255(18):8811–8818. [PubMed] [Google Scholar]
  25. Sullivan W. P., Smith D. F., Beito T. G., Krco C. J., Toft D. O. Hormone-dependent processing of the avian progesterone receptor. J Cell Biochem. 1988 Feb;36(2):103–119. doi: 10.1002/jcb.240360202. [DOI] [PubMed] [Google Scholar]
  26. Swanson M. S., Dreyfuss G. Classification and purification of proteins of heterogeneous nuclear ribonucleoprotein particles by RNA-binding specificities. Mol Cell Biol. 1988 May;8(5):2237–2241. doi: 10.1128/mcb.8.5.2237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Watt F. M. Involucrin and other markers of keratinocyte terminal differentiation. J Invest Dermatol. 1983 Jul;81(1 Suppl):100s–103s. doi: 10.1111/1523-1747.ep12540786. [DOI] [PubMed] [Google Scholar]
  28. Welch W. J., Feramisco J. R. Purification of the major mammalian heat shock proteins. J Biol Chem. 1982 Dec 25;257(24):14949–14959. [PubMed] [Google Scholar]
  29. Wessel D., Flügge U. I. A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal Biochem. 1984 Apr;138(1):141–143. doi: 10.1016/0003-2697(84)90782-6. [DOI] [PubMed] [Google Scholar]
  30. Wier M. L., Scott R. E. Polypeptide changes associated with loss of proliferative potential during the terminal event in differentiation. J Cell Biochem. 1987 Feb;33(2):137–150. doi: 10.1002/jcb.240330208. [DOI] [PubMed] [Google Scholar]
  31. Wier M. L., Scott R. E. Regulation of the terminal event in cellular differentiation: biological mechanisms of the loss of proliferative potential. J Cell Biol. 1986 May;102(5):1955–1964. doi: 10.1083/jcb.102.5.1955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wilk H. E., Angeli G., Schäfer K. P. In vitro reconstitution of 35S ribonucleoprotein complexes. Biochemistry. 1983 Sep 13;22(19):4592–4600. doi: 10.1021/bi00288a038. [DOI] [PubMed] [Google Scholar]
  33. Wilk H. E., Werr H., Friedrich D., Kiltz H. H., Schäfer K. P. The core proteins of 35S hnRNP complexes. Characterization of nine different species. Eur J Biochem. 1985 Jan 2;146(1):71–81. doi: 10.1111/j.1432-1033.1985.tb08621.x. [DOI] [PubMed] [Google Scholar]
  34. Wilke M. S., Hsu B. M., Scott R. E. Two subtypes of reversible cell cycle restriction points exist in cultured normal human keratinocyte progenitor cells. Lab Invest. 1988 Jun;58(6):660–666. [PubMed] [Google Scholar]
  35. Wille J. J., Jr, Pittelkow M. R., Shipley G. D., Scott R. E. Integrated control of growth and differentiation of normal human prokeratinocytes cultured in serum-free medium: clonal analyses, growth kinetics, and cell cycle studies. J Cell Physiol. 1984 Oct;121(1):31–44. doi: 10.1002/jcp.1041210106. [DOI] [PubMed] [Google Scholar]
  36. Wille J. J., Jr, Scott R. E. Suppression of tumorigenicity by the cell-cycle-dependent control of cellular differentiation and proliferation. Int J Cancer. 1986 Jun 15;37(6):875–881. doi: 10.1002/ijc.2910370613. [DOI] [PubMed] [Google Scholar]

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