Abstract

The rates of synthesis of the polyamines (spermidine and spermine) and their metabolic precursor putrescine are elevated during the proliferative response of mammalian cells. The cellular levels of two key enzymes of polyamine biosynthesis, ornithine decarboxylase, and S-adenosylmethionine decarboxylase, are greatly elevated early in the response of small lymphocytes to mitogenic activation. Initially, the studies have concentrated on regulation of S-adenosylmethionine decarboxylase. The enzyme has been purified and rabbit antiserum and mouse monoclonal antibodies have been prepared to it. We have measured the rate of synthesis in intact lymphocytes and it is stimulated 10-fold within 9 hrs after mitogenic activation. cDNA clones coding for S-adenosyl-methionine decarboxylase have been prepared using synthetic DNA probes, based on amino acid sequences from the protein to screen a bovine lymphocyte cDNA library. These recombinant DNA probes are being used to investigate the mechanism of translational and transcriptional control of this enzyme in mitogen-activated lymphocytes. (J)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039053-02
Application #
3177748
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Raney, Alexa; Law, G Lynn; Mize, Gregory J et al. (2002) Regulated translation termination at the upstream open reading frame in s-adenosylmethionine decarboxylase mRNA. J Biol Chem 277:5988-94
Law, G L; Raney, A; Heusner, C et al. (2001) Polyamine regulation of ribosome pausing at the upstream open reading frame of S-adenosylmethionine decarboxylase. J Biol Chem 276:38036-43
Mize, G J; Morris, D R (2001) A mammalian sequence-dependent upstream open reading frame mediates polyamine-regulated translation in yeast. RNA 7:374-81
Morris, D R; Geballe, A P (2000) Upstream open reading frames as regulators of mRNA translation. Mol Cell Biol 20:8635-42
Raney, A; Baron, A C; Mize, G J et al. (2000) In vitro translation of the upstream open reading frame in the mammalian mRNA encoding S-adenosylmethionine decarboxylase. J Biol Chem 275:24444-50
Brown, C Y; Mize, G J; Pineda, M et al. (1999) Role of two upstream open reading frames in the translational control of oncogene mdm2. Oncogene 18:5631-7
Link, A J; Eng, J; Schieltz, D M et al. (1999) Direct analysis of protein complexes using mass spectrometry. Nat Biotechnol 17:676-82
Mize, G J; Ruan, H; Low, J J et al. (1998) The inhibitory upstream open reading frame from mammalian S-adenosylmethionine decarboxylase mRNA has a strict sequence specificity in critical positions. J Biol Chem 273:32500-5
Ruan, H; Shantz, L M; Pegg, A E et al. (1996) The upstream open reading frame of the mRNA encoding S-adenosylmethionine decarboxylase is a polyamine-responsive translational control element. J Biol Chem 271:29576-82
Morris, D R (1995) Growth control of translation in mammalian cells. Prog Nucleic Acid Res Mol Biol 51:339-63

Showing the most recent 10 out of 29 publications