Phosphorylation and mannosylation of dolichol (C55) in microsomes from hepatocytes preincubated with dolichol

Chojnacki, Tadeusz; Ekström, Tomas J.; Dallner, Gustav

doi:10.1016/0014-5793(80)80595-3

Cited by 15 publications

(1 citation statement)

References 10 publications

(7 reference statements)

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“…The decrease in DNA synthesis could partially be reversed by the addition of dolichol-20 [Larsson et al, 1989]. Uptake of dolichol in cultured cells is welldocumented [Carson and Lennarz, 1979;Chojnacki et al, 1980;Rip et al, 1985;Dricu et al, 1997]. In another study we showed that dolichol could delay cell cycle arrest in human diploid fibroblasts when the HMG-CoA reductase activity was decreased [Larsson and Wejde, 1992].…”

Section: Discussionmentioning

confidence: 95%

Dolichol-like lipids with stimulatory effect on DNA synthesis: Substrates for protein dolichylation?

et al. 1998

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Substantial evidence has suggested that a nonsterol product of mevalonic acid (MVA) is essential for the initiation of DNA synthesis in mammalian cells. Several possible isoprenoid candidates have been suggested, but the identity of this compound still remains unknown. In this study we have isolated and purified MVA products from SV40-transformed human fibroblasts and identified fractions with a growth-stimulatory effect. The cells were labelled with [14C]MVA in the presence of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. After lipid extraction, the [14C]MVA-labelled lipids were subjected to high performance liquid chromatography and size-exclusion chromatography, and the effect of the fractionated eluate on the DNA synthesis of arrested MVA-depleted target cells was tested. Thereby we found a fraction of [14C]MVA-labelled lipids with a substantial stimulatory effect on DNA synthesis. The chromatographic behavior suggested that the growth-stimulating fractions contained dolichol-20. This was confirmed by mass spectrometric analysis. Similar results were obtained when lipids from hepatocellular carcinoma cells and a sample from breast tumor were isolated and analyzed by the same procedure. The mechanisms by which these compounds induce DNA synthesis are unknown. Recent data obtained in our laboratory have provided evidence that dolichyl groups are covalently linked to tumor cell proteins, which implicates a new biological function for long-chain polyisoprenoid alcohols (Hjertman et al. [1997] FEBS Lett 416:235-238). In this study we demonstrate that tumor cells containing dolichol-like growth-stimulatory lipids also contained dolichylated proteins. This raises the question whether the growth-stimulatory dolichol-like lipids serve as substrates for the dolichylation reaction.

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Section: Discussionmentioning

confidence: 95%

Dolichol-like lipids with stimulatory effect on DNA synthesis: Substrates for protein dolichylation?

et al. 1998

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Intracellular and Extracellular Flow of Dolichol

Dessel

Wolf

Hilderson

et al. 1990

Subcellular Biochemistry

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Uptake and metabolism of polyprenols by animal cells cultured in vitro

Krajewska

Jankowski

1981

Bioscience Reports

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Several mammalian, chicken, and mosquito cells grown in vitro take up tritiated dolichol supplied to the incubation medium. The extent of labelling varied markedly between different cell cultures. After 20 h incubation most of the dolichol taken up was unchanged and the major product of metabolism of dolichol was identified as its fatty acid esters. Green-monkey kidney cells were tested with 8 fully unsaturated and 6 alpha-saturated polyprenols ranging from C35 to C105. In general the uptake of alpha-saturated polyprenols (dolichol type, was higher. Considerable differences were found between the uptake of polyprenols of differing chain lengths. Less than 1% of the polyprenols taken up was converted into more polar product, mainly polyprenyl phosphates and polyprenyl phosphate sugars. The short-chain polyprenols, from C35 to C65, were metabolized more rapidly than the long-chain polyprenols, as judged from the amount of polar products and fatty acid esters of polyprenols.

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Phosphorylation and mannosylation of dolichol (C55) in microsomes from hepatocytes preincubated with dolichol

Cited by 15 publications

References 10 publications

Dolichol-like lipids with stimulatory effect on DNA synthesis: Substrates for protein dolichylation?

Dolichol-like lipids with stimulatory effect on DNA synthesis: Substrates for protein dolichylation?

Intracellular and Extracellular Flow of Dolichol

Uptake and metabolism of polyprenols by animal cells cultured in vitro

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