Post-translational incorporation of the antiproliferative agent azatyrosine into the C-terminus of alpha-tubulin.

PURRO, SILVIA A; BISIG CARLOS GASTÓN; CONTIN MARIA ANA; BARRA, HECTOR SILVIO; ARCE, CARLOS ANGEL

PORTLAND PRESS LTD

Lugar: New York; Año: 2003 vol. 375 p. 121 - 121

bstract Detyrosination/tyrosination of tubulin is a post-translational modification that occurs at the C-terminus of the alpha-subunit, giving rise to microtubules rich in either tyrosinated or detyrosinated tubulin which coexist in the cell. We hereby report that the tyrosine analogue, azatyrosine, can be incorporated into the C-terminus of alpha-tubulin instead of tyrosine. Azatyrosine is structurally identical to tyrosine except that a nitrogen atom replaces carbon-2 of the phenolic group. Azatyrosine competitively excluded incorporation of [14C]tyrosine into tubulin of soluble brain extract. A newly developed rabbit antibody specific to C-terminal azatyrosine was used to study incorporation of azatyrosine in cultured cells. When added to the culture medium (Ham's F12K), azatyrosine was incorporated into tubulin of glioma-derived C6 cells. This incorporation was reversible, i.e. after withdrawal of azatyrosine, tubulin lost azatyrosine and reincorporated tyrosine. Azatyrosinated t