Interaction between mevalonate pathway and retinoic acid-induced differentiation

All trans retinoic acid (ATRA) is a potent inducer of differentiation of HL-60 cell line. The pretreatment of the cells by compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl (HMG) CoA reductase, during 24 hours, enhances the ATRA-induced cell differentiation. At 50 nM, the percentage of cell differentiation is 34.9% ± 2 and 73% ± 2.96 in the control and compactin-treated cells, respectively. The removal of compactin boosts the level of HMG-CoA reductase and therefore the biosynthesis of sterol and nonsterol isoprenoid compounds. The participation of sterol and nonsterol pathway was then investigated. The supply of an excess of cholesterol (up to 80 μg/ml of LDL) leads to a significant decrease of cell differentiation by ATRA from 78% ± 0.1 to 54% ± 2.8. A concomitant decrease of cell growth (51% ± 6.4) was observed. The pretreatment of cells by the geranylgeranyltransferase inhibitor (GGTI-298) has no effect on the cell differentiation process. By contrast, the farnesyltransferase inhibitors (FTI-II and FTI-277) completely abolish the ATRA-induced differentiation, thus confirming the involvement of farnesylated proteins in the differentiation mechanism.

[1]  N. Gueddari,et al.  Enhancement of all-trans-retinoic acid efficiency in granulocytic differentiation of HL-60 cells by incorporation into low density lipoprotein. , 1998, International Journal of Oncology.

[2]  Marshall Cj,et al.  Reversion of a human tumour cell line containing oncogenic p21ras is associated with a defect in the post-translational processing of the ras protein. , 1995 .

[3]  N. Takahashi,et al.  Potential applications of cytodifferentiation therapy in hematologic malignancies. , 1994, Seminars in hematology (Print).

[4]  M. Lanotte,et al.  Two distinctly regulated events, priming and triggering, during retinoid-induced maturation and resistance of NB4 promyelocytic leukemia cell line. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[5]  P. Allen,et al.  Modulation of CD13 expression during retinoic acid-induced differentiation of HL60 cells. , 1994, Leukemia research.

[6]  P. Edwards,et al.  Identification of farnesol as the non-sterol derivative of mevalonic acid required for the accelerated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. , 1994, The Journal of biological chemistry.

[7]  J. Ericsson,et al.  Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins. , 1994, Biochimica et biophysica acta.

[8]  G. Prendergast,et al.  Farnesyltransferase inhibition causes morphological reversion of ras-transformed cells by a complex mechanism that involves regulation of the actin cytoskeleton , 1994, Molecular and cellular biology.

[9]  P. Edwards,et al.  Mevalonic acid-dependent degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in vivo and in vitro. , 1994, The Journal of biological chemistry.

[10]  M. Favata,et al.  Modulation of 3-hydroxy-3-methylglutaryl-CoA reductase by 15 alpha-fluorolanost-7-en-3 beta-ol. A mechanism-based inhibitor of cholesterol biosynthesis. , 1993, The Journal of biological chemistry.

[11]  J. Fruchart,et al.  Sequential ultracentrifugation micromethod for separation of serum lipoproteins and assays of lipids, apolipoproteins, and lipoprotein particles. , 1993, Clinical chemistry.

[12]  M. Andreeff,et al.  Induction of differentiation in myeloid leukemia cell lines and acute promyelocytic leukemia cells by liposomal all-trans-retinoic acid. , 1993, Cancer research.

[13]  C J Marshall,et al.  Protein prenylation: a mediator of protein-protein interactions. , 1993, Science.

[14]  P. Casey,et al.  Biochemistry of protein prenylation. , 1992, Journal of lipid research.

[15]  Gregor Eichele,et al.  9-cis retinoic acid is a high affinity ligand for the retinoid X receptor , 1992, Cell.

[16]  J. Grippo,et al.  9-Cis retinoic acid stereoisomer binds and activates the nuclear receptor RXRα , 1992, Nature.

[17]  T. Osborne.  Single nucleotide resolution of sterol regulatory region in promoter for 3-hydroxy-3-methylglutaryl coenzyme A reductase. , 1991, The Journal of biological chemistry.

[18]  R. Evans,et al.  Characterization of DNA binding and retinoic acid binding properties of retinoic acid receptor. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Gibbs.  Ras C-terminal processing enzymes—New drug targets? , 1991, Cell.

[20]  J. Brockes.  Reading the retinoid signals , 1990, Nature.

[21]  M. Gelb,et al.  Prenyl proteins in eukaryotic cells: a new type of membrane anchor. , 1990, Trends in biochemical sciences.

[22]  J. Goldstein,et al.  Regulation of the mevalonate pathway , 1990, Nature.

[23]  P. Casey,et al.  p21ras is modified by a farnesyl isoprenoid. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[24]  W. Schafer,et al.  Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans. , 1989, Science.

[25]  C. Marshall,et al.  All ras proteins are polyisoprenylated but only some are palmitoylated , 1989, Cell.

[26]  J. R. Smith,et al.  Multiple sterol regulatory elements in promoter for hamster 3-hydroxy-3-methylglutaryl-coenzyme A synthase. , 1988, The Journal of biological chemistry.

[27]  R. Evans,et al.  The steroid and thyroid hormone receptor superfamily. , 1988, Science.

[28]  T. Osborne,et al.  Operator constitutive mutation of 3-hydroxy-3-methylglutaryl coenzyme A reductase promoter abolishes protein binding to sterol regulatory element. , 1988, The Journal of biological chemistry.

[29]  S. Collins,et al.  Normal functional characteristics of cultured human promyelocytic leukemia cells (HL-60) after induction of differentiation by dimethylsulfoxide , 1979, The Journal of experimental medicine.

[30]  P. Fenaux,et al.  All-trans retinoic acid in acute promyelocytic leukemias. II. In vitro studies: structure-function relationship. , 1990, Blood.

[31]  C. Marshall,et al.  Reversion of a human tumour cell line containing oncogenic p21ras is associated with a defect in the post-translational processing of the ras protein. , 1995, Oncogene.

[32]  C. Farnsworth,et al.  Role of protein modification reactions in programming interactions between ras-related GTPases and cell membranes. , 1994, Annual review of cell biology.

[33]  C. Der,et al.  The ras/cholesterol connection: implications for ras oncogenicity. , 1992, Critical reviews in oncogenesis.

[34]  J. Brockes.  Developmental biology. Reading the retinoid signals. , 1990, Nature.