Angiogenin

Angiogenin (Ang) is a small polypeptide that is implicated in angiogenesis (formation of new blood vessels) in tumor growth . However, angiogenin is unique among the many proteins that are involved in angiogenesis in that it is also an enzyme with an amino acid sequence 33% identical to that of bovine pancreatic ribonuclease (RNase) A). Moreover, although Ang has the same general catalytic properties as RNase A - it cleaves preferentially on the 3' side of pyrimidines and follows a transphosphorylation/hydrolysis mechanism - its activity differs markedly both in magnitude and in specificity.

Although angiogenin contains counterparts for the key catalytic residues of bovine pancreatic RNase A, it cleaves standard RNase substrates 105 - 106 times less efficiently than does RNase A. Despite this apparent weakness, the enzymatic activity of Ang appears to be essential for biological activity: replacements of important active site residuesinvariably diminish ribonuclease and angiogenesis activities in parallel, and a substitution that increases enzymatic activity also enhances angiogenic potency.

Angiogenin may function as a tRNA-specific ribonuclease that binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus, thereby promoting the endothelial invasiveness necessary for blood vessel formation. Angiogenin induces vascularization of normal and malignant tissues, and abolishes protein synthesis by specifically hydrolyzing cellular tRNAs.

Alternative splicing results in two transcript variants encoding the same protein. This gene and the gene that encodes ribonuclease, RNase A family, 4 share promoters and 5' exons. Each gene splices to a unique downstream exon that contains its complete coding region. [cite web | title = Entrez Gene: ANG angiogenin, ribonuclease, RNase A family, 5| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=283| accessdate = ]

References

Further reading

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*cite journal | author=Saxena SK, Rybak SM, Davey RT, "et al." |title=Angiogenin is a cytotoxic, tRNA-specific ribonuclease in the RNase A superfamily. |journal=J. Biol. Chem. |volume=267 |issue= 30 |pages= 21982–6 |year= 1992 |pmid= 1400510 |doi=
*cite journal | author=Weremowicz S, Fox EA, Morton CC, Vallee BL |title=Localization of the human angiogenin gene to chromosome band 14q11, proximal to the T cell receptor alpha/delta locus. |journal=Am. J. Hum. Genet. |volume=47 |issue= 6 |pages= 973–81 |year= 1990 |pmid= 1978563 |doi=
*cite journal | author=Weremowicz S, Fox EA, Morton CC, Vallee BL |title=The placental ribonuclease inhibitor (RNH) gene is located on chromosome subband 11p15.5. |journal=Genomics |volume=8 |issue= 4 |pages= 717–21 |year= 1991 |pmid= 2276743 |doi=
*cite journal | author=Shapiro R, Riordan JF, Vallee BL |title=Characteristic ribonucleolytic activity of human angiogenin. |journal=Biochemistry |volume=25 |issue= 12 |pages= 3527–32 |year= 1986 |pmid= 2424496 |doi=
*cite journal | author=Weiner HL, Weiner LH, Swain JL |title=Tissue distribution and developmental expression of the messenger RNA encoding angiogenin. |journal=Science |volume=237 |issue= 4812 |pages= 280–2 |year= 1987 |pmid= 2440105 |doi=
*cite journal | author=Bicknell R, Vallee BL |title=Angiogenin activates endothelial cell phospholipase C. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=85 |issue= 16 |pages= 5961–5 |year= 1988 |pmid= 2457905 |doi=
*cite journal | author=Shapiro R, Vallee BL |title=Site-directed mutagenesis of histidine-13 and histidine-114 of human angiogenin. Alanine derivatives inhibit angiogenin-induced angiogenesis. |journal=Biochemistry |volume=28 |issue= 18 |pages= 7401–8 |year= 1990 |pmid= 2479414 |doi=
*cite journal | author=Bicknell R, Vallee BL |title=Angiogenin stimulates endothelial cell prostacyclin secretion by activation of phospholipase A2. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=86 |issue= 5 |pages= 1573–7 |year= 1989 |pmid= 2646638 |doi=
*cite journal | author=Lee FS, Vallee BL |title=Characterization of ribonucleolytic activity of angiogenin towards tRNA. |journal=Biochem. Biophys. Res. Commun. |volume=161 |issue= 1 |pages= 121–6 |year= 1989 |pmid= 2730651 |doi=
*cite journal | author=Lee FS, Vallee BL |title=Binding of placental ribonuclease inhibitor to the active site of angiogenin. |journal=Biochemistry |volume=28 |issue= 8 |pages= 3556–61 |year= 1989 |pmid= 2742853 |doi=
*cite journal | author=Strydom DJ, Fett JW, Lobb RR, "et al." |title=Amino acid sequence of human tumor derived angiogenin. |journal=Biochemistry |volume=24 |issue= 20 |pages= 5486–94 |year= 1986 |pmid= 2866794 |doi=
*cite journal | author=Kurachi K, Davie EW, Strydom DJ, "et al." |title=Sequence of the cDNA and gene for angiogenin, a human angiogenesis factor. |journal=Biochemistry |volume=24 |issue= 20 |pages= 5494–9 |year= 1986 |pmid= 2866795 |doi=
*cite journal | author=Shapiro R, Vallee BL |title=Human placental ribonuclease inhibitor abolishes both angiogenic and ribonucleolytic activities of angiogenin. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue= 8 |pages= 2238–41 |year= 1987 |pmid= 3470787 |doi=
*cite journal | author=Rybak SM, Fett JW, Yao QZ, Vallee BL |title=Angiogenin mRNA in human tumor and normal cells. |journal=Biochem. Biophys. Res. Commun. |volume=146 |issue= 3 |pages= 1240–8 |year= 1987 |pmid= 3619929 |doi=
*cite journal | author=Shapiro R, Strydom DJ, Olson KA, Vallee BL |title=Isolation of angiogenin from normal human plasma. |journal=Biochemistry |volume=26 |issue= 16 |pages= 5141–6 |year= 1987 |pmid= 3663649 |doi=
*cite journal | author=Hu GF, Strydom DJ, Fett JW, "et al." |title=Actin is a binding protein for angiogenin. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 4 |pages= 1217–21 |year= 1993 |pmid= 7679494 |doi=
*cite journal | author=Moroianu J, Riordan JF |title=Identification of the nucleolar targeting signal of human angiogenin. |journal=Biochem. Biophys. Res. Commun. |volume=203 |issue= 3 |pages= 1765–72 |year= 1994 |pmid= 7945327 |doi= 10.1006/bbrc.1994.2391
*cite journal | author=Moroianu J, Riordan JF |title=Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 5 |pages= 1677–81 |year= 1994 |pmid= 8127865 |doi=
*cite journal | author=Acharya KR, Shapiro R, Allen SC, "et al." |title=Crystal structure of human angiogenin reveals the structural basis for its functional divergence from ribonuclease. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue= 8 |pages= 2915–9 |year= 1994 |pmid= 8159679 |doi=
*cite journal | author=Hu GF, Riordan JF, Vallee BL |title=A putative angiogenin receptor in angiogenin-responsive human endothelial cells. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue= 6 |pages= 2204–9 |year= 1997 |pmid= 9122172 |doi=

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