Specific binding of human dihydrofolate reductase protein to dihydrofolate reductase messenger RNA in vitro

Chu, Edward; Takimoto, Chris H.; Voeller, Donna; Grem, Jean L.; Allegra, Carmen J.

doi:10.1021/bi00069a009

Cited by 130 publications

(89 citation statements)

References 37 publications

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“…Furthermore, MTX was shown to prevent this binding (14) and lead to an increase in DHFR protein expression. The nucleotide sequence to which DHFR protein binds DHFR mRNA within the coding domain is known (15,16), and the specific amino acids that DHFR protein utilizes to bind DHFR mRNA have been elucidated (17).…”

Section: Methotrexate (Mtx) Is An Anti-folate That Inhibits De Novo Pmentioning

confidence: 99%

Dihydrofolate Reductase and Thymidylate Synthase Transgenes Resistant to Methotrexate Interact to Permit Novel Transgene Regulation

Rushworth

Mathews

Alpert

et al. 2015

Journal of Biological Chemistry

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Background:Methotrexate targets dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS) to prevent cancer growth, and increases DHFR expression when applied. Results: TYMS resistant to methotrexate inhibits the methotrexate induced increase in DHFR expression. Conclusion: Thymidine synthesis regulates post-transcriptional expression of DHFR and TYMS. Significance: Methotrexate-resistant DHFR and TYMS can be used to regulate cis and trans transgene in primary T cells.

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Section: Methotrexate (Mtx) Is An Anti-folate That Inhibits De Novo Pmentioning

confidence: 99%

Dihydrofolate Reductase and Thymidylate Synthase Transgenes Resistant to Methotrexate Interact to Permit Novel Transgene Regulation

Rushworth

Mathews

Alpert

et al. 2015

Journal of Biological Chemistry

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“…This has been attributed to a phenomenon in which the DHFR message binds to DHFR, thus regulating its availability for translation. In the presence of an antifolate, the message is released, translation is enhanced, and synthesis of protein is increased (Chu et al, 1993;Ercikan et al, 1993;Ercikan-Abali et al, 1997;Schmitz et al, 2001). Regulation of DHFR expression by this mechanism was absent in the malaria parasite and suggested as a factor in the utility of antifolates in the treatment of this disease (Zhang and Rathod, 2002).…”

Section: Alterations In Dhfrmentioning

confidence: 99%

Resistance to antifolates

2003

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“…The well characterized iron regulatory protein, which is required for iron homeostasis in cells, is the cytosolic enzyme aconitase (12,48). The enzymes thymidylate synthase and dihydrofolate reductase bind to their own mRNAs and repress translation (15,16). The two glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase, bind to AU-rich elements in the 3Ј-untranslated regions of mRNAs (49,50).…”

Section: Fig 6 Mevalonate Kinase-depleted Lrbp Preparation Shows Dementioning

confidence: 99%

“…Studies have indicated the presence of cis-acting regulatory elements in the 5Ј-untranslated region, coding region, and 3Ј-untranslated region of mRNA (10). A number of cytoplasmic trans-acting factors, some of which shuttle between the nucleus and cytoplasm, have been identified as mRNA-stabilizing, destabilizing, or translational repressor proteins (11)(12)(13)(14)(15)(16). c-Fos, c-Myc, tropoelastin, thymidylate synthase, and dihydrofolate reductase are some of the mRNAs containing regulatory elements in the coding region for trans-acting factors (17)(18)(19)(20)(21)(22)(23)(24).…”

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confidence: 99%

Isolation and Characterization of a Novel trans-Factor for Luteinizing Hormone Receptor mRNA from Ovary

Nair

Menon

2004

Journal of Biological Chemistry

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Post-transcriptional mechanisms play a major role in regulating luteinizing hormone (LH) receptor mRNA expression in the ovary. An ovarian cytosolic protein that we have identified in rats and humans, which binds to a polypyrimidine-rich bipartitate sequence in the coding region of LHR mRNA, acts as a trans-acting factor in this process. In the present study, we isolated and characterized this LH receptor mRNA-binding protein (LRBP) from rat ovary. LRBP was purified to homogeneity by cation exchange chromatography followed by Northwestern analysis and subsequent elution of the single protein band from SDS-polyacrylamide gel. Purified LRBP was subjected to N-terminal microsequencing followed by homology search, which revealed its identity as mevalonate kinase. Purified rat mevalonate kinase antibody recognized the gel-purified LRBP on Western blots performed with one-and two-dimensional SDSpolyacrylamide gels. When recombinant mevalonate kinase produced in human embryonic kidney cells ( The interaction of luteinizing hormone (LH) 1 with its cell surface receptors controls reproductive functions including steroidogenesis in the gonad (1). In the ovary, luteinizing hormone receptor (LHR), a member of G s -protein coupled receptors, regulates ovarian function mainly through increased production of cAMP (2-4). The cell surface expression of LHR varies during different stages of the ovarian cycle. Its expression in granulosa cells and luteal cells is greatly decreased by an endogenous preovulatory LH surge or by the administration of a pharmacological dose of human chorionic gonadotropin (hCG), a placental counterpart of LH (5-8). We have shown that the decline in cell surface LHR expression seen after hCG administration is paralleled by a specific loss of all four LHR mRNA transcripts (6.7, 4.4, 2.6, and 1.8 kb) in the ovary (9). Furthermore, the loss of LHR mRNA does not result from decreased transcription but occurs post-transcriptionally with a 3-fold decrease in half-life (8).Regulation of mRNA turnover is one of the major control mechanisms of gene expression in all organisms. mRNA halflives are influenced by the interaction of various cytoplasmic proteins (trans-acting factors) with regulatory regions (cis-acting elements) in the mRNA, forming ribonucleoprotein (RNP) complexes (10). The formation and disruption of RNP complexes in response to various cellular stimuli mainly controls the turnover of cytoplasmic mRNA. Studies have indicated the presence of cis-acting regulatory elements in the 5Ј-untranslated region, coding region, and 3Ј-untranslated region of mRNA (10). A number of cytoplasmic trans-acting factors, some of which shuttle between the nucleus and cytoplasm, have been identified as mRNA-stabilizing, destabilizing, or translational repressor proteins (11-16). c-Fos, c-Myc, tropoelastin, thymidylate synthase, and dihydrofolate reductase are some of the mRNAs containing regulatory elements in the coding region for trans-acting factors (17-24).We have identified a LHR mRNA-binding protein in rat and hu...

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Specific binding of human dihydrofolate reductase protein to dihydrofolate reductase messenger RNA in vitro

Cited by 130 publications

References 37 publications

Dihydrofolate Reductase and Thymidylate Synthase Transgenes Resistant to Methotrexate Interact to Permit Novel Transgene Regulation

Dihydrofolate Reductase and Thymidylate Synthase Transgenes Resistant to Methotrexate Interact to Permit Novel Transgene Regulation

Resistance to antifolates

Isolation and Characterization of a Novel trans-Factor for Luteinizing Hormone Receptor mRNA from Ovary

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