Abstract
The terminal differentiation of erythroblasts during erythrocyte maturation entails significant cellular remodeling. In avian cells this is accomplished in part by marked attenuation of nuclear transcription and in mammalian cells by the physical extrusion of the nucleus. Thus lacking the ability to replace all but those proteins required for maintenance of the mature erythrocyte, the normal complement of cellular constituents is subsequently modified by a highly active degradative mechanism(s) to yield a sub-population of proteins stable to such proteolysis. During this time many metabolic pathways are shunted by selective turnover of key enzymes. The enhanced degradation essential to erythroid cell maturation is assumed to involve the same ATP, ubiquitin-dependent multi-enzyme pathway responsible for cytosolic protein turnover within all eukaryotes. The mechanism(s) required to commit erythroblasts to enhanced degradation and to direct the resulting selective degradation of key enzymes provides a tractable model for the less acute regulation observed within nucleated cells. Characterization of the ATP, ubiquitin-dependent pathway in erythroid cells and recent observations in other cells and tissues subject to enhanced degradation in response to various experimental manipulations provides some understanding of the dynamics exhibited by this system during terminal differentiation.
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References
A. Hershko, Ubiquitin-mediated protein degradation, J. Biol. Chem., 263:15237 (1988).
B. P. Monia, D. J. Ecker and S. T. Crooke, New prospective on the structure and function of ubiquitin, Biotechnol. 8:209 (1990).
A. Ciechanover, H. Heller, S. Elias, A. L. Haas and A. Hershko, ATP-dependent conjugation of reticulocyte proteins with the polypeptide required for protein degradation, Proc. Natl. Acad. Sci. U.S.A. 77:1365 (1980).
A. Hershko, A. Ciechanover, H. Heller, A. L. Haas and I. A. Rose, Proposed role of ATP in protein breakdown: Conjugation of proteins with multiple chains of the polypeptide of ATP-dependent proteolysis, Proc. Natl. Acad. Sci. U.S.A. 77:1783 (1980).
A. L. Haas, Immunochemical probes of ubiqutin pool dynamics, in: “Ubiquitin,” M. Rechsteiner, ed., Plenum Press, New York (1988).
C. M. Pickart, Ubiquitin activation and ligation, in: “Ubiquitin,” M. Rechsteiner, ed., Plenum Press, New York (1988).
A. L. Haas, K. E. Murphy and P. M. Bright, The inactivation of ubiquitin accounts for the inability to demonstrate ATP, ubiquitin-dependent proteolysis in liver extracts, J. Biol. Chem. 260:4694 (1985).
J. M. Fagan, L. Waxman and A. L. Goldberg, Skeletal muscle and liver contain a soluble ATP-ubiquitin-dependent proteolytic pathway, Biochem. J. 243:335 (1987).
A. L. Haas and P. M. Bright, The immunochemical detection and quantitation of intracellular ubiquitin-protein conjugates, J. Biol. Chem. 260:12464 (1985).
A. L. Haas, Role of ubiquitin in protein degradation, in: “Protein Metabolism in Aging,” H. L. Segal, M. Rothstein, and E. Bergamini, eds., Wiley-Liss, New York (1990).
A. L. Haas and P. M. Bright, The dynamics of ubiquitin pools within cultured human lung fibroblasts, J. Biol. Chem. 262:345 (1987).
A. L. Haas and I. A. Rose, The mechanism of ubiquitin activating enzyme, J. Biol. Chem. 257:10329 (1982).
V. Chau, J. W. Tobias, A. Bachmair, D. Marriott, D. J. Ecker, D. K. Gonda and A. Varshavsky, A multiubiquitin chain is confined to a specific lysine in a targeted short-lived protein, Science 243:1576 (1989).
A. L. Haas and I. A. Rose, Hemin inhibits ATP-dependent ubiquitin-dependent proteolysis: Role of hemin in regulating ubiquitin conjugate degradation, Proc. Natl. Acad. Sci. U.S.A. 78:6845 (1981).
A. L. Haas, P. M. Bright and V. Chau, Ubiquitin conjugation by the yeast RAD6 and CDC34 gene products, J. Biol. Chem., in press (1990).
A. Hershko, H. Heller, E. Eytan and Y. Reiss, The protein substrate binding site of the ubiquitin-protein ligase system, J. Biol. Chem. 261:11992 (1986).
R. L. Dunten and R. E. Cohen, Recognition of modified forms of ribonuclease A by the ubiquitin system, J. Biol. Chem. 264:16739 (1989).
A. Bachmair and A. Varshavsky, The degradation signal in a short-lived protein, Cell 56:1019 (1989).
A. Haas, R. M. Reback, G. Pratt and M. Rechsteiner, Ubiquitin-mediated degradation of histone H3 does not require the substrate binding protein E3 or attachment of polyubiquitin chains, J. Biol. Chem., in press (1990).
U. Bond, N. Agell, A. L. Haas, K. Redman and M. Schlesinger, Ubiquitin in stressed chicken embryo fibroblasts, J. Biol. Chem. 263:2384 (1988).
A. L. Haas, The dynamics of ubiquitin pools within skeletal muscle, in: “The Ubiquitin System,” M. Schlesinger and A. Hershko, eds., Cold Spring Harbor Laboratory, New York (1988).
U. Bond and M. Schlesinger, Ubiquitin is a heat shock protein in chicken embryo fibroblasts, Mol. Cell. Biol. 5:949 (1985).
L. M. Schwartz and J. W. Truman, Hormonal control of rates of metamorphic development in the tobacco hornworm Manduca sexta, Devel. Biol. 99:103 (1983).
A. Hershko, E. Eytan, A. Ciechanover and A. L. Haas, Immunochemical analysis of the turnover of ubiquitin-protein conjugates in intact cells, J. Biol. Chem. 257:13964 (1982).
N. T. Neff, L. Bourret, P. Miao and J. F. Dice, Degradation of proteins microinjected into IMR-90 human diploid fibroblasts, J. Cell. Biol. 91:184 (1981).
G. Pratt, R. Hough and M. Rechsteiner, Proteolysis in heat-stressed HeLa cells. Stabilization of ubiquitin correlates with the loss of proline endopeptidase, J. Biol. Chem. 246:12526 (1989).
L. Laszlo, F. J. Doherty, N. U. Osborn and R. J. Mayer, Ubiquitinated protein conjugates are specifically enriched in the lysosomal system of fibroblasts, FEBS Lett. 261:365 (1990).
S. Rapoport, W. Dubiel and M. Muller, Proteolysis of mitochondria in reticulocytes during maturation is ubiquitin-dependent and is accompanied by a high rate of ATP hydrolysis, FEBS Lett. 180:249 (1985).
A. L. Goldberg and F. S. Boches, Oxidized proteins in erythrocytes are rapidly degraded by the adenosine triphosphate-dependent proteolytic system, Science 215:1107 (1982).
D. T. Chin, L. Kuehl and M. Rechsteiner, Conjugation of ubiquitin to denatured hemoglobin is proportional to the rate of hemoglobin degradation in HeLa cells, Proc. Natl. Acad. Sci. U.S.A. 79:5857 (1982).
L. Gregori, D. Marriott, C. M. West and V. Chau, Specific recognition of calmodulin from Dictylostelium discoideum by the ATP, ubiquitin-dependent degradative pathway, J. Biol. Chem. 260:5232 (1985).
L. Gregori, D. Marriott, J. A. Putkey, A. R. Means and V. Chau, Bacterially synthesized vertebrate calmodulin is a specific substrate for ubiquitination, J. Biol. Chem. 262:2562 (1987).
J. R. Schaeffer, ATP-dependent proteolysis of hemoglobin a chains in ß-thalassemic hemolysates is ubiquitin-dependent, J. Biol. Chem. 263:13663 (1988).
D. A. Riley, J. L. W. Bain, S. Ellis and A. L. Haas, Quantitation and immunohistochemical localization of ubiquitin conjugates within rat red and white skeletal muscles, J. Histochem. Cytochem. 36:621 (1988).
C. M. Pickart and A. T. Vella, Levels of active ubiquitin carrier proteins decline during erythroid maturation, J. Biol. Chem. 263:12028 (1988).
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© 1991 Plenum Press, New York
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Haas, A.L. (1991). Ubiquitin-Mediated Processes in Erythroid Cell Maturation. In: Magnani, M., De Flora, A. (eds) Red Blood Cell Aging. Advances in Experimental Medicine and Biology, vol 307. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5985-2_18
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DOI: https://doi.org/10.1007/978-1-4684-5985-2_18
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