New polypeptide with palmitoyltransferase activity, useful e.g. for treatment and diagnosis of cancer and metabolic disease, also nucleic acid encoding it and antibodies

摘要

Isolated polypeptide (I) that binds palmitoyl-coenzyme A and functions as a palmitoyltransferase is new. (I) is: (i) a 200 amino acid (aa) sequence (2), reproduced; or (ii) an allele or derivative formed from (2) by substitution, deletion, insertion or inversion of aa. Independent claims are also included for the following: (1) isolated nucleic acid (II) that encodes (I) and is: (i) a 603 bp sequence (1), reproduced, or its complements or fragments; (ii) sequence that wholly or partially hybridizes to (ii); or (iii) the RNA equivalent of (i) or (ii); (2) recombinant DNA vector that contains (II) and is suitable for expression or amplification in prokaryotic or eukaryotic cells; and (3) antibodies (Ab) specific for (I). ACTIVITY : Cytostatic. No details of tests for cytostatic activity are given. MECHANISM OF ACTION : Modulating activity or expression of palmitoyltransferase, involved in palmitoylation of protein, a process that causes proteins to be anchored firmly in membranes and is essential for activity of some signal-tranduction proteins, e.g. the products of the proto-oncogenes Ras and Src. Vacuoles were isolated from the yeast strain BJ3505 and incubated for 10 minutes at 26[deg]C in presence of cytosol, coenzyme A and tritium-labeled palmitate, then separated and the palmitoylated vacuolar protein Vac8p determined by gel electrophoresis and fluorography. Antibodies against (I) reduced palmitoylation of Vac8 to less than 20% of its control value and reduced vacuolar fusion to below 10% of the control value. Recombinant (I) had a similar inhibitory effect.