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Effects of the farnesyltransferase inhibitor UCF‐1C/manumycin on growth and p21‐ras post‐translational processing in NIH3T3 cells
Author(s) -
Servais Patricia,
Gulbis Béatrice,
Fokan Dominique,
Galand Paul
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980518)76:4<601::aid-ijc25>3.0.co;2-8
Subject(s) - farnesyltransferase , prenylation , farnesyltransferase inhibitor , transfection , oncogene , cell growth , biology , microbiology and biotechnology , rac1 , gene , biochemistry , enzyme , chemistry , signal transduction , cell cycle
Examination of the effect of the farnesylprotein transferase (FPTase) inhibitor UCF1‐C/manumycin on NIH3T3 cells transfected with a normal N‐ ras gene and expressing high levels of the corresponding p21‐ras protein showed that 10 μm UCF1‐C immediately and reversibly inhibited growth in these cells, without modifying cell‐death rate, thus acting as a cytostatic. There was also a 98% reduction of p21‐ras neo‐farnesylation and a 3‐fold decrease in total content in p21‐ras products, yet without gross modification of the relative content in the post‐translational products and without accumulation of the native protein to detectable levels. UCF1‐C likewise reversibly inhibited growth in parental NIH3T3 cells, as well as in sub‐strains expressing a transfected normal or mutated H‐ ras gene. Together with the fact that the well‐developed network of actin stress fibers present in the NIH3T3 (N‐ ras ) cells was not affected by the FPTase inhibitor, these data indicate that its growth‐inhibitory effect is not necessarily in direct relation with that exerted on p21‐ras processing. Alternatively, it might be causally related to the decreased prenylation of other cellular proteins, perhaps included among the 13 proteins, unrelated to p21‐ras, of which the farnesylation was also reduced under UCF1‐C treatment. Some cells transformed by a ras or non‐ras oncogene might exhibit higher susceptibility towards FPTase inhibitors than normal cells, but this might then be attributable to differences in the pattern of expression and/or in the functional importance of non‐ras farnesylated proteins. Int. J. Cancer 76:601–608, 1998.© 1998 Wiley‐Liss, Inc.