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Proc Natl Acad Sci U S A. Dec 1984; 81(23): 7476–7480.
PMCID: PMC392169

Specific stimulation of actin gene transcription by epidermal growth factor and cycloheximide.


Stimulation of quiescent AKR-2B mouse embryo cells with epidermal growth factor (EGF) results in a rapid and specific induction of actin mRNA sequences. These mRNAs include those coding for both beta- and gamma-cytoskeletal, but not alpha-skeletal muscle, actin isotypes. Elongation of nascent RNA chains in isolated nuclei (run-off transcription) demonstrates that the mRNA accumulation is preceded by an increase in actin gene transcription. This increase is transient, however, and is followed by a rapid attenuation of transcriptional activity. An inhibitor of protein synthesis, cycloheximide, was also found to induce beta- and gamma-actin mRNA accumulation. Furthermore, the simultaneous addition of EGF and cycloheximide produced a synergistic effect on actin sequences in both steady-state nuclear and polysomal RNA. Run-off transcription experiments demonstrate that this synergistic effect results from an increase in the magnitude and duration of actin gene transcription. It is also specific in that alpha-tubulin gene transcription is not similarly affected. These data suggest the existence of a specific labile repressor of actin gene transcription.

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  • Fox CF, Linsley PS, Wrann M. Receptor remodeling and regulation in the action of epidermal growth factor. Fed Proc. 1982 Nov;41(13):2988–2995. [PubMed]
  • Wells DJ, Stoddard LS, Getz MJ, Moses HL. alpha-Amanitin and 5-fluorouridine inhibition of serum-stimulated DNA synthesis in quiescent AKR-2B mouse embryo cells. J Cell Physiol. 1979 Aug;100(2):199–214. [PubMed]
  • Carpenter G, Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216. [PubMed]
  • Das M, Fox CF. Molecular mechanism of mitogen action: processing of receptor induced by epidermal growth factor. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2644–2648. [PMC free article] [PubMed]
  • Getz MJ, Elder PK, Benz EW, Jr, Stephens RE, Moses HL. Effect of cell proliferation on levels and diversity of poly(A)-containing mRNA. Cell. 1976 Feb;7(2):255–65. [PubMed]
  • Williams JG, Penman S. The messenger RNA sequences in growing and resting mouse fibroblasts. Cell. 1975 Oct;6(2):197–206. [PubMed]
  • Cochran BH, Reffel AC, Stiles CD. Molecular cloning of gene sequences regulated by platelet-derived growth factor. Cell. 1983 Jul;33(3):939–947. [PubMed]
  • Linzer DI, Nathans D. Growth-related changes in specific mRNAs of cultured mouse cells. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4271–4275. [PMC free article] [PubMed]
  • Lin S, Riggs AD. The general affinity of lac repressor for E. coli DNA: implications for gene regulation in procaryotes and eucaryotes. Cell. 1975 Feb;4(2):107–111. [PubMed]
  • Kelly K, Cochran BH, Stiles CD, Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983 Dec;35(3 Pt 2):603–610. [PubMed]
  • Riddle VG, Dubrow R, Pardee AB. Changes in the synthesis of actin and other cell proteins after stimulation of serum-arrested cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1298–1302. [PMC free article] [PubMed]
  • Hodgson CP, Elder PK, Ono T, Foster DN, Getz MJ. Structure and expression of mouse VL30 genes. Mol Cell Biol. 1983 Dec;3(12):2221–2231. [PMC free article] [PubMed]
  • Stallcup MR, Ring J, Yamamoto KR. Synthesis of mouse mammary tumor virus ribonucleic acid in isolated nuclei from cultured mammary tumor cells. Biochemistry. 1978 Apr 18;17(8):1515–1521. [PubMed]
  • Shipley GD, Childs CB, Volkenant ME, Moses HL. Differential effects of epidermal growth factor, transforming growth factor, and insulin on DNA and protein synthesis and morphology in serum-free cultures of AKR-2B cells. Cancer Res. 1984 Feb;44(2):710–716. [PubMed]
  • Benz EW, Jr, Getz MJ, Wells DJ, Moses HL. Nuclear RNA polymerase activities and poly(A)-containing mRNA accumulation in cultured AKR mouse embryo cells stimulated to proliferate. Exp Cell Res. 1977 Aug;108(1):157–165. [PubMed]
  • Minty AJ, Alonso S, Guénet JL, Buckingham ME. Number and organization of actin-related sequences in the mouse genome. J Mol Biol. 1983 Jun 15;167(1):77–101. [PubMed]
  • Ponte P, Gunning P, Blau H, Kedes L. Human actin genes are single copy for alpha-skeletal and alpha-cardiac actin but multicopy for beta- and gamma-cytoskeletal genes: 3' untranslated regions are isotype specific but are conserved in evolution. Mol Cell Biol. 1983 Oct;3(10):1783–1791. [PMC free article] [PubMed]
  • Vandekerckhove J, Weber K. Actin typing on total cellular extracts: a highly sensitive protein-chemical procedure able to distinguish different actins. Eur J Biochem. 1981 Jan;113(3):595–603. [PubMed]
  • McKnight GS, Palmiter RD. Transcriptional regulation of the ovalbumin and conalbumin genes by steroid hormones in chick oviduct. J Biol Chem. 1979 Sep 25;254(18):9050–9058. [PubMed]
  • Nguyen-Huu MC, Sippel AA, Hynes NE, Groner B, Schütz G. Preferential transcription of the ovalbumin gene in isolated hen oviduct nuclei by RNA polymerase B. Proc Natl Acad Sci U S A. 1978 Feb;75(2):686–690. [PMC free article] [PubMed]
  • Bitter GA, Roeder RG. Transcription of viral genes by RNA polymerase II in nuclei isolated from adenovirus 2 transformed cells. Biochemistry. 1978 May 30;17(11):2198–2205. [PubMed]
  • Murdoch GH, Potter E, Nicolaisen AK, Evans RM, Rosenfeld MG. Epidermal growth factor rapidly stimulates prolactin gene transcription. Nature. 1982 Nov 11;300(5888):192–194. [PubMed]
  • Cleveland DW, Lopata MA, MacDonald RJ, Cowan NJ, Rutter WJ, Kirschner MW. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. [PubMed]
  • Meister RK, Hulman SE, Johnson LF. Rapid changes in poly (A)(+) mRNA content in growth stimulated fibroblasts following perturbations in protein synthesis. J Cell Physiol. 1979 Sep;100(3):531–538. [PubMed]
  • Supowit SC, Potter E, Evans RM, Rosenfeld MG. Polypeptide hormone regulation of gene transcription: specific 5' genomic sequences are required for epidermal growth factor and phorbol ester regulation of prolactin gene expression. Proc Natl Acad Sci U S A. 1984 May;81(10):2975–2979. [PMC free article] [PubMed]
  • Leavitt J, Leavitt A, Attallah AM. Dissimilar modes of expression of beta- and gamma-actin in normal and leukemic human T lymphocytes. J Biol Chem. 1980 Jun 10;255(11):4984–4987. [PubMed]
  • Garrels JI, Gibson W. Identification and characterization of multiple forms of actin. Cell. 1976 Dec;9(4 Pt 2):793–805. [PubMed]
  • Maness PF, Walsh RC., Jr Dihydrocytochalasin B disorganizes actin cytoarchitecture and inhibits initiation of DNA synthesis in 3T3 cells. Cell. 1982 Aug;30(1):253–262. [PubMed]
  • Pollack R, Osborn M, Weber K. Patterns of organization of actin and myosin in normal and transformed cultured cells. Proc Natl Acad Sci U S A. 1975 Mar;72(3):994–998. [PMC free article] [PubMed]
  • Boschek CB, Jockusch BM, Friis RR, Back R, Grundmann E, Bauer H. Early changes in the distribution and organization of microfilament proteins during cell transformation. Cell. 1981 Apr;24(1):175–184. [PubMed]
  • Bushman FD, Crain WR., Jr Conserved pattern of embryonic actin gene expression in several sea urchins and a sand dollar. Dev Biol. 1983 Aug;98(2):429–436. [PubMed]
  • Schafer U, Golden L, Hyman LE, Colot HV, Rosbash M. Some somatic sequences are absent or exceedingly rare in Xenopus oocyte RNA. Dev Biol. 1982 Nov;94(1):87–92. [PubMed]
  • Sodja A, Arking R, Zafar RS. Actin gene expression during embryogenesis of Drosophila melanogaster. Dev Biol. 1982 Apr;90(2):363–368. [PubMed]
  • Giebelhaus DH, Heikkila JJ, Schultz GA. Changes in the quantity of histone and actin messenger RNA during the development of preimplantation mouse embryos. Dev Biol. 1983 Jul;98(1):148–154. [PubMed]
  • Farmer SR, Wan KM, Ben-Ze'ev A, Penman S. Regulation of actin mRNA levels and translation responds to changes in cell configuration. Mol Cell Biol. 1983 Feb;3(2):182–189. [PMC free article] [PubMed]
  • Spiegelman BM, Farmer SR. Decreases in tubulin and actin gene expression prior to morphological differentiation of 3T3 adipocytes. Cell. 1982 May;29(1):53–60. [PubMed]
  • Naharro G, Robbins KC, Reddy EP. Gene product of v-fgr onc: hybrid protein containing a portion of actin and a tyrosine-specific protein kinase. Science. 1984 Jan 6;223(4631):63–66. [PubMed]
  • Campisi J, Gray HE, Pardee AB, Dean M, Sonenshein GE. Cell-cycle control of c-myc but not c-ras expression is lost following chemical transformation. Cell. 1984 Feb;36(2):241–247. [PubMed]
  • Ringold GM, Dieckmann B, Vannice JL, Trahey M, McCormick F. Inhibition of protein synthesis stimulates the transcription of human beta-interferon genes in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1984 Jul;81(13):3964–3968. [PMC free article] [PubMed]

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