Regulation of mouse ornithine decarboxylase activity by cell growth, serum and tetradecanoyl phorbol acetate is governed primarily by sequences within the coding region of the gene

Abstract

To determine the genetic elements required for modulation of ornithine decarboxylase (ODC) activity in response to cell growth or treatment with serum or with tetradecanoyl phorbol acetate, ODCdeficient cells were transfected with a series of recombinant DNAs encoding mouse ODC. All of the transfected cells expressing an intact mouse ODC protein displayed regulation of ODC activity, including those expressing a construct deprived of all ODC-specific sequence information except the protein-coding region. ODC mRNA changed much less than enzymatic activity. A mutation of the protein-coding region that converted ODC from an unstable to a stable intracellular protein attenuated the regulatory response. We conclude that post-transcriptional events associated with ODC degradation dominate the response to these stimuli.

Induction of ornithine decarboxylase by IL-3 is mediated by sequential c-Myc-independent and c-Myc-dependent pathways

“…A modest induction of ODC mRNA was also observed within 1 h of IL-3 stimulation, yet levels of ODC transcripts continued to accumulate during the 12 h time course of the experiment. As previously reported in other cells (Van Dalen Wetters et al, 1989), cycloheximide alone induced modest levels of ODC RNA, and ODC levels were further elevated in cells treated with cycloheximide plus IL-3, relative to cells treated with IL-3 (Figure 4a). However, after 3 h, cycloheximide prevented the continued accumulation of ODC RNA observed in cells treated with IL-3 alone.…”

“…In IL-3 stimulated 32D.3 and FDC-P1.2 myeloid cells, induction of ODC RNA is delayed relative to cmyc RNA, more consistent with a delayed early response (Akew et al, 1991). However, ODC regulation has also previously been reported to contain an immediate early component Van Dalen Wetters et al, 1989). To resolve this issue, we analysed the kinetics of induction of c-myc and ODC RNAs in IL-3 stimulated FDC-P1.2 cells, in the presence or absence of cycloheximide to inhibit protein synthesis.…”

“…cyclin A, p53 and cad). However, expression of the best characterized target of c-Myc, ornithine decarboxylase (ODC) (Askew et al, 1991;Bello-Fernandez et al, 1993;Packham and Cleveland, 1994;PenÄ a et al, 1994;Tavtigian et al, 1994;Tobias et al, 1995;Wagner et al, 1993), is (like c-Myc) independent of cell cycle phase in growing cells yet modulated by mitogen withdrawal or stimulation (Askew et al, 1991;Bowlin et al, 1986;Van Dalen Wetters et al, 1989). ODC catalyzes the conversion of ornithine to putrescine, a rate limiting step in the biosynthesis of putrescine and the polyamines spermidine and spermine (Pegg, 1986).…”

“…Although expression of ODC, like c-Myc, is regulated at many levels, increased transcription is an important component of the response to mitogens Van Dalen Wetters et al, 1989). However, the control of ODC transcription is complex and in addition to c-Myc, members of several other families of transcription factors have been demonstrated to regulate the transcription of the ODC promoter, including cAMP dependent factors, c-Fos, steroid hormones and IRF-1 (Abrahamsen et al, 1992;Manzella et al, 1994;Moshier et al, 1992;Wrighton and Busslinger, 1993).…”

Angoline and Chelerythrine, Benzophenanthridine Alkaloids That Do Not Inhibit Protein Kinase C

“…Activity is controlled by various factors, including expression, stability and transcription rate of ODC mRNA, stability and translation rate of the ODC enzyme, and post-translational modifications (27,28). Using mouse 308 cells as a model system, chelerythrine did not inhibit TPA-induced ODC activity within the non-cytotoxic range (IC 50 Ͼ1.0 g/ml), but promoted a slight enhancement of activity at lower concentrations.…”