A Dimeric Mutant of Human Pancreatic Ribonuclease with Selective Cytotoxicity Toward Malignant Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Jul 8

PMID 10393896

Citations 14

Authors

R Piccoli

S Di Gaetano

C De Lorenzo

M Grauso

C Monaco

D Spalletti-Cernia

P Laccetti

J Cinatl

J Matousek

G DAlessio

Affiliations

Soon will be listed here.

Abstract

Monomeric human pancreatic RNase, devoid of any biological activity other than its RNA degrading ability, was engineered into a dimeric protein with a cytotoxic action on mouse and human tumor cells, but lacking any appreciable toxicity on mouse and human normal cells. This dimeric variant of human pancreas RNase selectively sensitizes to apoptotic death cells derived from a human thyroid tumor. Because of its selectivity for tumor cells, and because of its human origin, this protein represents a potentially very attractive, novel tool for anticancer therapy.

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References

Kunkel T . Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985; 82(2):488-92. PMC: 397064. DOI: 10.1073/pnas.82.2.488. View

Adinolfi B, Cafaro V, DAlessio G, Di Donato A . Full antitumor action of recombinant seminal ribonuclease depends on the removal of its N-terminal methionine. Biochem Biophys Res Commun. 1995; 213(2):525-32. DOI: 10.1006/bbrc.1995.2163. View

Parente A, Merrifield B, Geraci G, DAlessio G . Molecular basis of superreactivity of cysteine residues 31 and 32 of seminal ribonuclease. Biochemistry. 1985; 24(5):1098-104. DOI: 10.1021/bi00326a005. View

Ciglic M, Jackson P, Raillard S, Haugg M, Jermann T, Opitz J . Origin of dimeric structure in the ribonuclease superfamily. Biochemistry. 1998; 37(12):4008-22. DOI: 10.1021/bi972203e. View

Weickmann J, ELSON M, Glitz D . Purification and characterization of human pancreatic ribonuclease. Biochemistry. 1981; 20(5):1272-8. DOI: 10.1021/bi00508a035. View

Moore A, SABACHEWSKY L, Toolan H . Culture characteristics of four permanent lines of human cancer cells. Cancer Res. 1955; 15(9):598-602. View

KUNITZ M . A spectrophotometric method for the measurement of ribonuclease activity. J Biol Chem. 2010; 164(2):563-8. View

Kim J, Soucek J, Matousek J, Raines R . Mechanism of ribonuclease cytotoxicity. J Biol Chem. 1995; 270(52):31097-102. DOI: 10.1074/jbc.270.52.31097. View

Cinatl J, Mainke M, Weissflog A, Rabenau H, Kornhuber B, Doerr H . In vitro differentiation of human neuroblastoma cells induced by sodium phenylacetate. Cancer Lett. 1993; 70(1-2):15-24. DOI: 10.1016/0304-3835(93)90069-l. View

10.

Russo N, de Nigris M, Ciardiello A, Di Donato A, DAlessio G . Expression in mammalian cells, purification and characterization of recombinant human pancreatic ribonuclease. FEBS Lett. 1993; 333(3):233-7. DOI: 10.1016/0014-5793(93)80660-m. View

11.

Friedman H, Burger P, Bigner S, Trojanowski J, Wikstrand C, Halperin E . Establishment and characterization of the human medulloblastoma cell line and transplantable xenograft D283 Med. J Neuropathol Exp Neurol. 1985; 44(6):592-605. DOI: 10.1097/00005072-198511000-00005. View

12.

Tanaka J, Ogura T, Sato H, Hatano M . Establishment and biological characterization of an in vitro human cytomegalovirus latency model. Virology. 1987; 161(1):62-72. DOI: 10.1016/0042-6822(87)90171-1. View

13.

Mastronicola M, Piccoli R, DAlessio G . Key extracellular and intracellular steps in the antitumor action of seminal ribonuclease. Eur J Biochem. 1995; 230(1):242-9. DOI: 10.1111/j.1432-1033.1995.tb20557.x. View

14.

Khatib Z, Matsushime H, Valentine M, Shapiro D, Sherr C, Look A . Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas. Cancer Res. 1993; 53(22):5535-41. View

15.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

16.

KANTOR G, Mulkie J, Hull D . A study of the effect of ultraviolet light on the division potential of human diploid fibroblasts. Exp Cell Res. 1978; 113(2):283-94. DOI: 10.1016/0014-4827(78)90368-3. View

17.

Laccetti P, Portella G, Mastronicola M, Russo A, Piccoli R, DAlessio G . In vivo and in vitro growth-inhibitory effect of bovine seminal ribonuclease on a system of rat thyroid epithelial transformed cells and tumors. Cancer Res. 1992; 52(17):4582-6. View

18.

Boix E, Wu Y, Vasandani V, Saxena S, Ardelt W, Ladner J . Role of the N terminus in RNase A homologues: differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity. J Mol Biol. 1996; 257(5):992-1007. DOI: 10.1006/jmbi.1996.0218. View

19.

DAlessio G . New and cryptic biological messages from RNases. Trends Cell Biol. 1993; 3(4):106-9. DOI: 10.1016/0962-8924(93)90166-x. View

20.

de Nigris M, Russo N, Piccoli R, DAlessio G, Di Donato A . Expression of bovine seminal ribonuclease in Escherichia coli. Biochem Biophys Res Commun. 1993; 193(1):155-60. DOI: 10.1006/bbrc.1993.1603. View