Relationship Between in Vivo Degradative Rates and Isoelectric Points of Proteins

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1975 Oct 1

PMID 1060070

Citations 49

Authors

J F Dice

A L GOLDBERG

Affiliations

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Abstract

Previous studies have shown that in mammalian cells proteins of large molecular weight are degraded more rapidly than small ones. Evidence is presented here that half-lives of proteins are also related to their isoelectric points. A double-isotope method was used to compare degradative rates of soluble proteins separated by isoelectric focusing. In rat liver, skeletal muscle, kidney, and brain, more rapid rates of catabolism were found for acidic protein fractions than for neutral or basic ones. Acidic proteins also tended to be degraded faster in several mouse tissues. A literature survey confirmed this trend. For 22 proteins from rat liver, a highly significant correlation was found between rates of degradation and isoelectric points (r = 0.824; P less than 0.01). This relationship between isoelectric point and half-life appears to be distinct from that between protein size and half-life.

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References

GOLDBERG A, Dice J . Intracellular protein degradation in mammalian and bacterial cells. Annu Rev Biochem. 1974; 43(0):835-69. DOI: 10.1146/annurev.bi.43.070174.004155. View

Noe B, BAUER G . Further characterization of a glucagon precursor from anglerfish islet tissue. Proc Soc Exp Biol Med. 1973; 142(1):210-3. DOI: 10.3181/00379727-142-36990. View

GOLDBERG A . Degradation of abnormal proteins in Escherichia coli (protein breakdown-protein structure-mistranslation-amino acid analogs-puromycin). Proc Natl Acad Sci U S A. 1972; 69(2):422-6. PMC: 426471. DOI: 10.1073/pnas.69.2.422. View

Lin C, Orcutt M, FISHMAN W . Purification and characterization of mouse kidney beta-glucuronidase. J Biol Chem. 1975; 250(12):4737-43. View

Lin S, Zabin I . Beta-galactosidase. Rates of synthesis and degradation of incomplete chains. J Biol Chem. 1972; 247(7):2205-11. View

Kemper B, Habener J, Potts Jr J, Rich A . Proparathyroid hormone: identification of a biosynthetic precursor to parathyroid hormone. Proc Natl Acad Sci U S A. 1972; 69(3):643-7. PMC: 426526. DOI: 10.1073/pnas.69.3.643. View

Schimke R, SWEENEY E, Berlin C . THE ROLES OF SYNTHESIS AND DEGRADATION IN THE CONTROL OF RAT LIVER TRYPTOPHAN PYRROLASE. J Biol Chem. 1965; 240:322-31. View

Kosuge T, Kamiya H . A new cyclic dipeptide from peptone. Nature. 1960; 188:1112. DOI: 10.1038/1881112a0. View

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

10.

FRITZ P, White E, Pruitt K, Vesell E . Lactate dehydrogenase isozymes. Turnover in rat heart, skeletal muscle, and liver. Biochemistry. 1973; 12(21):4034-9. DOI: 10.1021/bi00745a003. View

11.

Righetti P, DRYSDALE J . Small-scale fractionation of proteins and nucleic acids by isoelectric focusing in polyacrylamide gels. Ann N Y Acad Sci. 1973; 209:163-86. DOI: 10.1111/j.1749-6632.1973.tb47527.x. View

12.

Bond J . A comparison of the proteolytic susceptibility of several rat liver enzymes. Biochem Biophys Res Commun. 1971; 43(2):333-9. DOI: 10.1016/0006-291x(71)90757-1. View

13.

GOLDBERG A . Correlation between rates of degradation of bacterial proteins in vivo and their sensitivity to proteases. Proc Natl Acad Sci U S A. 1972; 69(9):2640-4. PMC: 427006. DOI: 10.1073/pnas.69.9.2640. View

14.

Smith C, VELICK S . The glyceraldehyde 3-phosphate dehydrogenases of liver and muscle. Cooperative interactions and conditions for functional reversibility. J Biol Chem. 1972; 247(1):273-84. View

15.

Munn E . Purification and some properties of cytoplasmic aspartate aminotransferase from sheep liver. Biochem J. 1973; 135(4):683-93. PMC: 1165884. DOI: 10.1042/bj1350683. View

16.

Ballard F, Hopgood M . Phosphopyruvate carboxylase induction by L-tryptophan. Effects on synthesis and degradation of the enzyme. Biochem J. 1973; 136(2):259-64. PMC: 1165951. DOI: 10.1042/bj1360259. View

17.

SUSOR W, Kochman M, Rutter W . Heterogeneity of presumably homogeneous protein preparations. Science. 1969; 165(3899):1260-2. DOI: 10.1126/science.165.3899.1260. View

18.

Litwack G, Rosenfield S . Coenzyme dissociation, a possible determinant of short half-life of inducible enzymes in mammalian liver. Biochem Biophys Res Commun. 1973; 52(1):181-8. DOI: 10.1016/0006-291x(73)90971-6. View

19.

Bagshaw J, DRYSDALE J, Malt R . Multiple forms of mammalian RNA polymerase displayed by gel electrofocusing. Ann N Y Acad Sci. 1973; 209:363-71. DOI: 10.1111/j.1749-6632.1973.tb47540.x. View

20.

SEGAL H, Matsuzawa T, Haider M, ABRAHAM G . What determines the half-life of proteins in vivo? Some experiences with alanine aminotransferase of rat tissues. Biochem Biophys Res Commun. 1969; 36(5):764-70. DOI: 10.1016/0006-291x(69)90675-5. View