Abstract
A theory is presented proposing that genetic regulation in mammalian cells is at least a two-tiered effect; that one level of regulation involves the transition between gene exposure and sequestration; that normal differentiation requires a different spectrum of genes to be exposed in each separate state of differentiation; that the fiber systems of the cell cytoskeleton and the nuclear matrix together control the degree of gene exposure; that specific phosphorylation of these elements causes them to assume a different organizational network and to impose a different pattern of sequestration and exposure on the elements of the genome; that the varied gene phosphorylation mechanisms in the cell are integrated in this function; that attachment of this network system to specific parts of the chromosomes brings about sequestration or exposure of the genes in their neighborhood in a fashion similar to that observed when microtubule elements attach through the kinetochore to the centromeric DNA; that one function of repetitive sequences is to serve as elements for the final attachment of this fibrous network to the specific chromosomal loci; and that at least an important part of the calcium manifestation as a metabolic trigger of different differentiation states involves its acting as a binding agent to centers of electronegativity, in particular proteins and especially phosphorylated groups, so as to change the conformation of the fiber network that ultimately controls gene exposure in the mammalian cell. It would appear essential to determine what abnormal gene exposures and sequestrations are characteristic of each type of cancer; which agonists, if any, will bring about reverse transformation; and whether these considerations can be used in therapy.
Similar content being viewed by others
Literature cited
Hsie, A.W., and Puck, T.T. (1971).Proc. Natl. Acad. Sci. U.S.A. 68358–361.
Porter, K.R., Puck, T.T., Hsie, A.W., and Kelley, D. (1974).Cell 2145–162.
Hsie, A.W., Jones, C., and Puck, T.T. (1971).Proc. Natl. Acad. Sci. U.S.A. 681648–1652.
Puck, T.T., and Jones, C. (1973). InCyclic AMP, Cell Growth and the Immune Response (eds.) Braun, W., Lichtenstein, L.M. and Parker, C.W. (Springer-Verlag, New York) pp. 338–348.
Puck, T.T. (1976).Dev. Genet. 372–80.
Puck, T.T. (1977). InCancer Biology IV, Differentiation and Carcinogenesis (eds.) Borek, C., Fenoglio, C.M. and King, D.W. (Stratton Books, New York), pp. 4–17.
Puck, T.T. (1977). InEucaryotic Genetics System (eds.) Wilcox, G., Abelson, J. and Fox, C.F. (Academic Press, New York), pp. 399–411.
Puck, T.T. (1977).Proc. Natl. Acad. Sci. U.S.A. 744491–4495.
Kao, F.T., Faik, P., and Puck, T.T. (1979).Exp. Cell Res. 12283–91.
Meek, W., and Puck, T.T. (1979).J. Supramol. Struct. 12335–354.
Meek, W.D., Porter, K.R., and Puck, T.T. (1980).Exp. Cell Res. 126359–374.
Puck, T.T., Erikson, R.L., Meek, W.D., and Nielson, S.E. (1981).J. Cell. Physiol. 107399–412.
Rumsby, G., and Puck, T.T. (1982).J. Cell. Physiol. 111133–139.
Schonberg, S., Patterson, D., and Puck, T.T. (1983).Exp. Cell Res. 14557–62.
Puck, T.T. (1984).Adv. Viral Oncol. 4197–216.
Ashall, F., and Puck, T.T. (1984).Proc. Natl. Acad. Sci. U.S.A. 815145–5149.
Ashall, F., Sullivan, N., and Puck, T.T. (1988).Proc. Natl. Acad. Sci. U.S.A. 853908–3912.
Chan, D., Goate, A., and Puck, T.T. (1989).Proc. Natl. Acad. Sci. U.S.A. 862747–2751.
Puck, T.T. (1989). InA Memorial Colloquium Honoring Herbert L. Anderson, August 31, 1988 (ed.) Metropolis, N. (Los Alamos National Laboratory, Los Alamos, New Mexico), pp. 9–15.
Storrie, B. (1975).J. Cell Biol. 66392–403.
Gabrielson, E.G., Scoggin, C., and Puck, T.T. (1982).Exp. Cell Res. 14263–68.
Miranti, C., and Puck, T.T. (1990).Somat. Cell Mol. Genet. 1667–77.
Puck, T.T. (1973). InThe Role of Cyclic Nucleotides in Carcinogenesis (eds.) Schultz, J. and Gratzner, H.G. (Academic Press, New York), pp. 283–302.
Puck, T.T. (1977). InThe Molecular Biology of the Mammalian Genetic Apparatus (ed.) Ts'o, P. (Elsevier North-Holland Biomedical Press, Amsterdam), pp. 171–180.
Bunn, P.A., Dienhart, D.G., Chan, D., Puck, T.T., Tagawa, M., Jewett, P.B., and Braunschweiger, E. (1990).Proc. Natl. Acad. Sci. U.S.A. 872162–2166.
Nielson, S.E., and Puck, T.T. (1980).Proc. Natl. Acad. Sci. U.S.A. 77985–989.
Johnson, G.S., Friedman, R.M., and Pastan, I. (1971).Proc. Natl. Acad. Sci. U.S.A. 68425–429.
Puck, T.T., Erikson, R.L., Meek, W.D., and Nielson, S.E. (1981).J. Cell. Physiol. 107399–412.
Huang, F.L., and Cho-Chung, Y.S. (1984).Biochem. Biophys. Res. Commun. 123141–147.
Moore, E.E., Moritz, E.A., and Mitra, N.W. (1985).Cancer Res. 454387–4396.
Krystosek, A., and Puck, T.T. (1989).J. Cell Biol. 109:231a.
Berridge, M.J., and Galione, A. (1988).FASEB J. 23074–3082.
Georgatos, S.D., and Blobel, G. (1987).J. Cell Biol. 105105–115.
Burridge, K., Fath, K., Kelly, T., Nuckolls, G., and Turner, C. (1988).Annu. Rev. Cell Biol. 4487–525.
Burridge, K., and Fath, K. (1989).Bioessays 10104–108.
Steinert, P.M., and Parry, D.A.D. (1985).Annu. Rev. Cell Biol. 141–65.
Osborn, M., and Weber, K. (1982).Cell 31303–306.
Maccioni, R.B. (1986).Revisiones Biol. Celular 81–103.
Worman, H.J., Lazaridis I., and Georgatos, S.D. (1988).J. Biol. Chem. 26312135–12141.
Fey, E.G., and Penman, S. (1988).Proc. Natl. Acad. Sci. U.S.A. 85121–125.
Georgatos, S.D., and Blobel, G. (1987).J. Cell Biol. 105117–125.
Prescott, D.M., and Bender, M.A. (1962).Exp. Cell Res. 26260–268.
Weintraub, H., and Groudine, M. (1976).Science 193848–856.
Garel, A., and Axel, R. (1976).Proc. Natl. Acad. Sci. U.S.A. 733966–3970.
Anderson, J.N., Vanderbilt, J.N., Lawson, G.M., Tsai, M.J., and O'Malley, B.W. (1983).Biochemistry 2221–29.
Maschek, U., Pulm, W., Segal, S., and Hammerling, G.J. (1989).Mol. Cell. Biol. 93136–3142.
Law, M.L., Gao, J., and Puck, T.T. (1989).Proc. Natl. Acad. Sci. U.S.A. 868472–8476.
Berenblum, I. (1954).Cancer Res. 14471–477.
Castagna, M., et al. (1982).J. Cell Biol. 2577847–7851.
Puck, T.T., Morkovin, D., Marcus, P.I., and Cieciura, S.J. (1957).J. Exp. Med. 106485–500.
Huebner, K., Linnenbach, A., Weidner, S., Glenn, G., and Croce, C.M. (1981).Proc. Natl. Acad. Sci. U.S.A. 785701–5075.
Szabo, G., Damjanovich, S., Sumegi, J., and Klein, G. (1987).Exp. Cell Res. 169158–168.
Cheung, W.Y. (1980).Science 20719–27.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Puck, T.T., Krystosek, A. & Chan, D.C. Genome regulation in mammalian cells. Somat Cell Mol Genet 16, 257–265 (1990). https://doi.org/10.1007/BF01233362
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01233362