Mimosine targets serine hydroxymethyltransferase.

Published

Journal Article

The plant amino acid, mimosine, is an extremely effective inhibitor of DNA replication in mammalian cells (Mosca, P. J., Dijkwel, P. A., and Hamlin, J. L. (1992) Mol. Cell. Biol. 12, 4375-4383). Mimosine appears to prevent the formation of replication forks at early-firing origins when delivered to mammalian cells approaching the G1/S boundary, and blocks DNA replication when added to S phase cells after a lag of approximately 2.5 h. We have shown previously that [3H]mimosine can be specifically photocross-linked both in vivo and in vitro to a 50-kDa polypeptide (p50) in Chinese hamster ovary (CHO) cells. In the present study, six tryptic peptides (58 residues total) from p50 were sequenced by tandem mass spectrometry and their sequences were found to be at least 77.5% identical and 96.5% similar to sequences in rabbit mitochondrial serine hydroxymethyltransferase (mSHMT). This assignment was verified by precipitating the [3H]mimosine-p50 complex with a polyclonal antibody to rabbit cSHMT. The 50-kDa cross-linked product was almost undetectable in a mimosine-resistant CHO cell line and in a CHO gly- cell line that lacks mitochondrial, but not cytosolic, SHMT activity. The gly- cell line is still sensitive to mimosine, suggesting that the drug may inhibit both the mitochondrial and the cytosolic forms. SHMT is involved in the penultimate step of thymidylate biosynthesis in mammalian cells and, as such, is a potential target for chemotherapy in the treatment of cancer.

Full Text

Duke Authors

Cited Authors

  • Lin, HB; Falchetto, R; Mosca, PJ; Shabanowitz, J; Hunt, DF; Hamlin, JL

Published Date

  • February 2, 1996

Published In

Volume / Issue

  • 271 / 5

Start / End Page

  • 2548 - 2556

PubMed ID

  • 8576220

Pubmed Central ID

  • 8576220

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.271.5.2548

Language

  • eng

Conference Location

  • United States