Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1996 Oct;16(10):5772–5781. doi: 10.1128/mcb.16.10.5772

Mad proteins contain a dominant transcription repression domain.

D E Ayer 1, C D Laherty 1, Q A Lawrence 1, A P Armstrong 1, R N Eisenman 1
PMCID: PMC231578  PMID: 8816491

Abstract

Transcription repression by the basic region-helix-loop-helix-zipper (bHLHZip) protein Mad1 requires DNA binding as a ternary complex with Max and mSin3A or mSin3B, the mammalian orthologs of the Saccharomyces cerevisiae transcriptional corepressor SIN3. The interaction between Mad1 and mSin3 is mediated by three potential amphipathic alpha-helices: one in the N terminus of Mad (mSin interaction domain, or SID) and two within the second paired amphipathic helix domain (PAH2) of mSin3A. Mutations that alter the structure of the SID inhibit in vitro interaction between Mad and mSin3 and inactivate Mad's transcriptional repression activity. Here we show that a 35-residue region containing the SID represents a dominant repression domain whose activity can be transferred to a heterologous DNA binding region. A fusion protein comprising the Mad1 SID linked to a Ga14 DNA binding domain mediates repression of minimal as well as complex promoters dependent on Ga14 DNA binding sites. In addition, the SID represses the transcriptional activity of linked VP16 and c-Myc transactivation domains. When fused to a full-length c-Myc protein, the Mad1 SID specifically represses both c-Myc's transcriptional and transforming activities. Fusions between the GAL DNA binding domain and full-length mSin3 were also capable of repression. We show that the association between Mad1 and mSin3 is not only dependent on the helical SID but is also dependent on both putative helices of the mSin3 PAH2 region, suggesting that stable interaction requires all three helices. Our results indicate that the SID is necessary and sufficient for transcriptional repression mediated by the Mad protein family and that SID repression is dominant over several distinct transcriptional activators.

Full Text

The Full Text of this article is available as a PDF (551.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abate C., Luk D., Curran T. Transcriptional regulation by Fos and Jun in vitro: interaction among multiple activator and regulatory domains. Mol Cell Biol. 1991 Jul;11(7):3624–3632. doi: 10.1128/mcb.11.7.3624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abate C., Luk D., Gagne E., Roeder R. G., Curran T. Fos and jun cooperate in transcriptional regulation via heterologous activation domains. Mol Cell Biol. 1990 Oct;10(10):5532–5535. doi: 10.1128/mcb.10.10.5532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Amati B., Brooks M. W., Levy N., Littlewood T. D., Evan G. I., Land H. Oncogenic activity of the c-Myc protein requires dimerization with Max. Cell. 1993 Jan 29;72(2):233–245. doi: 10.1016/0092-8674(93)90663-b. [DOI] [PubMed] [Google Scholar]
  4. Amati B., Dalton S., Brooks M. W., Littlewood T. D., Evan G. I., Land H. Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max. Nature. 1992 Oct 1;359(6394):423–426. doi: 10.1038/359423a0. [DOI] [PubMed] [Google Scholar]
  5. Auble D. T., Hansen K. E., Mueller C. G., Lane W. S., Thorner J., Hahn S. Mot1, a global repressor of RNA polymerase II transcription, inhibits TBP binding to DNA by an ATP-dependent mechanism. Genes Dev. 1994 Aug 15;8(16):1920–1934. doi: 10.1101/gad.8.16.1920. [DOI] [PubMed] [Google Scholar]
  6. Ayer D. E., Eisenman R. N. A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. Genes Dev. 1993 Nov;7(11):2110–2119. doi: 10.1101/gad.7.11.2110. [DOI] [PubMed] [Google Scholar]
  7. Ayer D. E., Kretzner L., Eisenman R. N. Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell. 1993 Jan 29;72(2):211–222. doi: 10.1016/0092-8674(93)90661-9. [DOI] [PubMed] [Google Scholar]
  8. Ayer D. E., Lawrence Q. A., Eisenman R. N. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell. 1995 Mar 10;80(5):767–776. doi: 10.1016/0092-8674(95)90355-0. [DOI] [PubMed] [Google Scholar]
  9. Bello-Fernandez C., Packham G., Cleveland J. L. The ornithine decarboxylase gene is a transcriptional target of c-Myc. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7804–7808. doi: 10.1073/pnas.90.16.7804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Benvenisty N., Leder A., Kuo A., Leder P. An embryonically expressed gene is a target for c-Myc regulation via the c-Myc-binding sequence. Genes Dev. 1992 Dec;6(12B):2513–2523. doi: 10.1101/gad.6.12b.2513. [DOI] [PubMed] [Google Scholar]
  11. Bernards R. Transcriptional regulation. Flipping the Myc switch. Curr Biol. 1995 Aug 1;5(8):859–861. doi: 10.1016/s0960-9822(95)00173-4. [DOI] [PubMed] [Google Scholar]
  12. Blackwood E. M., Eisenman R. N. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science. 1991 Mar 8;251(4998):1211–1217. doi: 10.1126/science.2006410. [DOI] [PubMed] [Google Scholar]
  13. Carlson M., Laurent B. C. The SNF/SWI family of global transcriptional activators. Curr Opin Cell Biol. 1994 Jun;6(3):396–402. doi: 10.1016/0955-0674(94)90032-9. [DOI] [PubMed] [Google Scholar]
  14. Cerni C., Bousset K., Seelos C., Burkhardt H., Henriksson M., Lüscher B. Differential effects by Mad and Max on transformation by cellular and viral oncoproteins. Oncogene. 1995 Aug 3;11(3):587–596. [PubMed] [Google Scholar]
  15. Chen J. D., Evans R. M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995 Oct 5;377(6548):454–457. doi: 10.1038/377454a0. [DOI] [PubMed] [Google Scholar]
  16. Chen J., Willingham T., Margraf L. R., Schreiber-Agus N., DePinho R. A., Nisen P. D. Effects of the MYC oncogene antagonist, MAD, on proliferation, cell cycling and the malignant phenotype of human brain tumour cells. Nat Med. 1995 Jul;1(7):638–643. doi: 10.1038/nm0795-638. [DOI] [PubMed] [Google Scholar]
  17. Chin L., Schreiber-Agus N., Pellicer I., Chen K., Lee H. W., Dudast M., Cordon-Cardo C., DePinho R. A. Contrasting roles for Myc and Mad proteins in cellular growth and differentiation. Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8488–8492. doi: 10.1073/pnas.92.18.8488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Courey A. J., Tjian R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell. 1988 Dec 2;55(5):887–898. doi: 10.1016/0092-8674(88)90144-4. [DOI] [PubMed] [Google Scholar]
  19. Cowell I. G., Hurst H. C. Transcriptional repression by the human bZIP factor E4BP4: definition of a minimal repression domain. Nucleic Acids Res. 1994 Jan 11;22(1):59–65. doi: 10.1093/nar/22.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Côté J., Quinn J., Workman J. L., Peterson C. L. Stimulation of GAL4 derivative binding to nucleosomal DNA by the yeast SWI/SNF complex. Science. 1994 Jul 1;265(5168):53–60. doi: 10.1126/science.8016655. [DOI] [PubMed] [Google Scholar]
  21. Delgado M. D., Lerga A., Cañelles M., Gómez-Casares M. T., León J. Differential regulation of Max and role of c-Myc during erythroid and myelomonocytic differentiation of K562 cells. Oncogene. 1995 Apr 20;10(8):1659–1665. [PubMed] [Google Scholar]
  22. Eagle L. R., Yin X., Brothman A. R., Williams B. J., Atkin N. B., Prochownik E. V. Mutation of the MXI1 gene in prostate cancer. Nat Genet. 1995 Mar;9(3):249–255. doi: 10.1038/ng0395-249. [DOI] [PubMed] [Google Scholar]
  23. Fondell J. D., Brunel F., Hisatake K., Roeder R. G. Unliganded thyroid hormone receptor alpha can target TATA-binding protein for transcriptional repression. Mol Cell Biol. 1996 Jan;16(1):281–287. doi: 10.1128/mcb.16.1.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gaubatz S., Meichle A., Eilers M. An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc. Mol Cell Biol. 1994 Jun;14(6):3853–3862. doi: 10.1128/mcb.14.6.3853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gidoni D., Kadonaga J. T., Barrera-Saldaña H., Takahashi K., Chambon P., Tjian R. Bidirectional SV40 transcription mediated by tandem Sp1 binding interactions. Science. 1985 Nov 1;230(4725):511–517. doi: 10.1126/science.2996137. [DOI] [PubMed] [Google Scholar]
  26. Gregor P. D., Sawadogo M., Roeder R. G. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev. 1990 Oct;4(10):1730–1740. doi: 10.1101/gad.4.10.1730. [DOI] [PubMed] [Google Scholar]
  27. Gu B., Kuddus R., DeLuca N. A. Repression of activator-mediated transcription by herpes simplex virus ICP4 via a mechanism involving interactions with the basal transcription factors TATA-binding protein and TFIIB. Mol Cell Biol. 1995 Jul;15(7):3618–3626. doi: 10.1128/mcb.15.7.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Gu W., Cechova K., Tassi V., Dalla-Favera R. Opposite regulation of gene transcription and cell proliferation by c-Myc and Max. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2935–2939. doi: 10.1073/pnas.90.7.2935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Hengartner C. J., Thompson C. M., Zhang J., Chao D. M., Liao S. M., Koleske A. J., Okamura S., Young R. A. Association of an activator with an RNA polymerase II holoenzyme. Genes Dev. 1995 Apr 15;9(8):897–910. doi: 10.1101/gad.9.8.897. [DOI] [PubMed] [Google Scholar]
  30. Henriksson M., Lüscher B. Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv Cancer Res. 1996;68:109–182. doi: 10.1016/s0065-230x(08)60353-x. [DOI] [PubMed] [Google Scholar]
  31. Hurlin P. J., Foley K. P., Ayer D. E., Eisenman R. N., Hanahan D., Arbeit J. M. Regulation of Myc and Mad during epidermal differentiation and HPV-associated tumorigenesis. Oncogene. 1995 Dec 21;11(12):2487–2501. [PubMed] [Google Scholar]
  32. Hurlin P. J., Quéva C., Koskinen P. J., Steingrímsson E., Ayer D. E., Copeland N. G., Jenkins N. A., Eisenman R. N. Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J. 1995 Nov 15;14(22):5646–5659. doi: 10.1002/j.1460-2075.1995.tb00252.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Hörlein A. J., När A. M., Heinzel T., Torchia J., Gloss B., Kurokawa R., Ryan A., Kamei Y., Söderström M., Glass C. K. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995 Oct 5;377(6548):397–404. doi: 10.1038/377397a0. [DOI] [PubMed] [Google Scholar]
  34. Imbalzano A. N., Kwon H., Green M. R., Kingston R. E. Facilitated binding of TATA-binding protein to nucleosomal DNA. Nature. 1994 Aug 11;370(6489):481–485. doi: 10.1038/370481a0. [DOI] [PubMed] [Google Scholar]
  35. Kasten M. M., Ayer D. E., Stillman D. J. SIN3-dependent transcriptional repression by interaction with the Mad1 DNA-binding protein. Mol Cell Biol. 1996 Aug;16(8):4215–4221. doi: 10.1128/mcb.16.8.4215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kato G. J., Barrett J., Villa-Garcia M., Dang C. V. An amino-terminal c-myc domain required for neoplastic transformation activates transcription. Mol Cell Biol. 1990 Nov;10(11):5914–5920. doi: 10.1128/mcb.10.11.5914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Keleher C. A., Redd M. J., Schultz J., Carlson M., Johnson A. D. Ssn6-Tup1 is a general repressor of transcription in yeast. Cell. 1992 Feb 21;68(4):709–719. doi: 10.1016/0092-8674(92)90146-4. [DOI] [PubMed] [Google Scholar]
  38. Kirschbaum B. J., Pognonec P., Roeder R. G. Definition of the transcriptional activation domain of recombinant 43-kilodalton USF. Mol Cell Biol. 1992 Nov;12(11):5094–5101. doi: 10.1128/mcb.12.11.5094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Koleske A. J., Young R. A. An RNA polymerase II holoenzyme responsive to activators. Nature. 1994 Mar 31;368(6470):466–469. doi: 10.1038/368466a0. [DOI] [PubMed] [Google Scholar]
  40. Koskinen P. J., Ayer D. E., Eisenman R. N. Repression of Myc-Ras cotransformation by Mad is mediated by multiple protein-protein interactions. Cell Growth Differ. 1995 Jun;6(6):623–629. [PubMed] [Google Scholar]
  41. Kretzner L., Blackwood E. M., Eisenman R. N. Myc and Max proteins possess distinct transcriptional activities. Nature. 1992 Oct 1;359(6394):426–429. doi: 10.1038/359426a0. [DOI] [PubMed] [Google Scholar]
  42. Kretzner L., Blackwood E. M., Eisenman R. N. Transcriptional activities of the Myc and Max proteins in mammalian cells. Curr Top Microbiol Immunol. 1992;182:435–443. doi: 10.1007/978-3-642-77633-5_55. [DOI] [PubMed] [Google Scholar]
  43. Kwon H., Imbalzano A. N., Khavari P. A., Kingston R. E., Green M. R. Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex. Nature. 1994 Aug 11;370(6489):477–481. doi: 10.1038/370477a0. [DOI] [PubMed] [Google Scholar]
  44. Lahoz E. G., Xu L., Schreiber-Agus N., DePinho R. A. Suppression of Myc, but not E1a, transformation activity by Max-associated proteins, Mad and Mxi1. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5503–5507. doi: 10.1073/pnas.91.12.5503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Larsson L. G., Pettersson M., Oberg F., Nilsson K., Lüscher B. Expression of mad, mxi1, max and c-myc during induced differentiation of hematopoietic cells: opposite regulation of mad and c-myc. Oncogene. 1994 Apr;9(4):1247–1252. [PubMed] [Google Scholar]
  46. Lee W., Haslinger A., Karin M., Tjian R. Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature. 1987 Jan 22;325(6102):368–372. doi: 10.1038/325368a0. [DOI] [PubMed] [Google Scholar]
  47. Li L. H., Nerlov C., Prendergast G., MacGregor D., Ziff E. B. c-Myc represses transcription in vivo by a novel mechanism dependent on the initiator element and Myc box II. EMBO J. 1994 Sep 1;13(17):4070–4079. doi: 10.1002/j.1460-2075.1994.tb06724.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Li Y., Bjorklund S., Jiang Y. W., Kim Y. J., Lane W. S., Stillman D. J., Kornberg R. D. Yeast global transcriptional regulators Sin4 and Rgr1 are components of mediator complex/RNA polymerase II holoenzyme. Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10864–10868. doi: 10.1073/pnas.92.24.10864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Lin Y. S., Carey M. F., Ptashne M., Green M. R. GAL4 derivatives function alone and synergistically with mammalian activators in vitro. Cell. 1988 Aug 26;54(5):659–664. doi: 10.1016/s0092-8674(88)80010-2. [DOI] [PubMed] [Google Scholar]
  50. Meichle A., Philipp A., Eilers M. The functions of Myc proteins. Biochim Biophys Acta. 1992 Dec 16;1114(2-3):129–146. doi: 10.1016/0304-419x(92)90011-m. [DOI] [PubMed] [Google Scholar]
  51. Paroush Z., Finley R. L., Jr, Kidd T., Wainwright S. M., Ingham P. W., Brent R., Ish-Horowicz D. Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins. Cell. 1994 Dec 2;79(5):805–815. doi: 10.1016/0092-8674(94)90070-1. [DOI] [PubMed] [Google Scholar]
  52. Philipp A., Schneider A., Väsrik I., Finke K., Xiong Y., Beach D., Alitalo K., Eilers M. Repression of cyclin D1: a novel function of MYC. Mol Cell Biol. 1994 Jun;14(6):4032–4043. doi: 10.1128/mcb.14.6.4032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Prendergast G. C., Lawe D., Ziff E. B. Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Cell. 1991 May 3;65(3):395–407. doi: 10.1016/0092-8674(91)90457-a. [DOI] [PubMed] [Google Scholar]
  54. Rao G., Alland L., Guida P., Schreiber-Agus N., Chen K., Chin L., Rochelle J. M., Seldin M. F., Skoultchi A. I., DePinho R. A. Mouse Sin3A interacts with and can functionally substitute for the amino-terminal repression of the Myc antagonist Mxi1. Oncogene. 1996 Mar 7;12(5):1165–1172. [PubMed] [Google Scholar]
  55. Roussel M. F., Ashmun R. A., Sherr C. J., Eisenman R. N., Ayer D. E. Inhibition of cell proliferation by the Mad1 transcriptional repressor. Mol Cell Biol. 1996 Jun;16(6):2796–2801. doi: 10.1128/mcb.16.6.2796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Sauer F., Fondell J. D., Ohkuma Y., Roeder R. G., Jäckle H. Control of transcription by Krüppel through interactions with TFIIB and TFIIE beta. Nature. 1995 May 11;375(6527):162–164. doi: 10.1038/375162a0. [DOI] [PubMed] [Google Scholar]
  57. Sawadogo M., Roeder R. G. Interaction of a gene-specific transcription factor with the adenovirus major late promoter upstream of the TATA box region. Cell. 1985 Nov;43(1):165–175. doi: 10.1016/0092-8674(85)90021-2. [DOI] [PubMed] [Google Scholar]
  58. Schreiber-Agus N., Chin L., Chen K., Torres R., Rao G., Guida P., Skoultchi A. I., DePinho R. A. An amino-terminal domain of Mxi1 mediates anti-Myc oncogenic activity and interacts with a homolog of the yeast transcriptional repressor SIN3. Cell. 1995 Mar 10;80(5):777–786. doi: 10.1016/0092-8674(95)90356-9. [DOI] [PubMed] [Google Scholar]
  59. Song W., Treich I., Qian N., Kuchin S., Carlson M. SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II. Mol Cell Biol. 1996 Jan;16(1):115–120. doi: 10.1128/mcb.16.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sterneck E., Müller C., Katz S., Leutz A. Autocrine growth induced by kinase type oncogenes in myeloid cells requires AP-1 and NF-M, a myeloid specific, C/EBP-like factor. EMBO J. 1992 Jan;11(1):115–126. doi: 10.1002/j.1460-2075.1992.tb05034.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Stillman D. J., Dorland S., Yu Y. Epistasis analysis of suppressor mutations that allow HO expression in the absence of the yeast SW15 transcriptional activator. Genetics. 1994 Mar;136(3):781–788. doi: 10.1093/genetics/136.3.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Stone J., de Lange T., Ramsay G., Jakobovits E., Bishop J. M., Varmus H., Lee W. Definition of regions in human c-myc that are involved in transformation and nuclear localization. Mol Cell Biol. 1987 May;7(5):1697–1709. doi: 10.1128/mcb.7.5.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Taunton J., Hassig C. A., Schreiber S. L. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science. 1996 Apr 19;272(5260):408–411. doi: 10.1126/science.272.5260.408. [DOI] [PubMed] [Google Scholar]
  64. Thompson C. M., Koleske A. J., Chao D. M., Young R. A. A multisubunit complex associated with the RNA polymerase II CTD and TATA-binding protein in yeast. Cell. 1993 Jul 2;73(7):1361–1375. doi: 10.1016/0092-8674(93)90362-t. [DOI] [PubMed] [Google Scholar]
  65. Torres R., Schreiber-Agus N., Morgenbesser S. D., DePinho R. A. Myc and Max: a putative transcriptional complex in search of a cellular target. Curr Opin Cell Biol. 1992 Jun;4(3):468–474. doi: 10.1016/0955-0674(92)90013-3. [DOI] [PubMed] [Google Scholar]
  66. Treitel M. A., Carlson M. Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3132–3136. doi: 10.1073/pnas.92.8.3132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Tzamarias D., Struhl K. Distinct TPR motifs of Cyc8 are involved in recruiting the Cyc8-Tup1 corepressor complex to differentially regulated promoters. Genes Dev. 1995 Apr 1;9(7):821–831. doi: 10.1101/gad.9.7.821. [DOI] [PubMed] [Google Scholar]
  68. Tzamarias D., Struhl K. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Nature. 1994 Jun 30;369(6483):758–761. doi: 10.1038/369758a0. [DOI] [PubMed] [Google Scholar]
  69. Um M., Li C., Manley J. L. The transcriptional repressor even-skipped interacts directly with TATA-binding protein. Mol Cell Biol. 1995 Sep;15(9):5007–5016. doi: 10.1128/mcb.15.9.5007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Vojtek A. B., Hollenberg S. M., Cooper J. A. Mammalian Ras interacts directly with the serine/threonine kinase Raf. Cell. 1993 Jul 16;74(1):205–214. doi: 10.1016/0092-8674(93)90307-c. [DOI] [PubMed] [Google Scholar]
  71. Västrik I., Kaipainen A., Penttilä T. L., Lymboussakis A., Alitalo R., Parvinen M., Alitalo K. Expression of the mad gene during cell differentiation in vivo and its inhibition of cell growth in vitro. J Cell Biol. 1995 Mar;128(6):1197–1208. doi: 10.1083/jcb.128.6.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Wang H., Clark I., Nicholson P. R., Herskowitz I., Stillman D. J. The Saccharomyces cerevisiae SIN3 gene, a negative regulator of HO, contains four paired amphipathic helix motifs. Mol Cell Biol. 1990 Nov;10(11):5927–5936. doi: 10.1128/mcb.10.11.5927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Wang H., Stillman D. J. In vitro regulation of a SIN3-dependent DNA-binding activity by stimulatory and inhibitory factors. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9761–9765. doi: 10.1073/pnas.87.24.9761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Wang H., Stillman D. J. Transcriptional repression in Saccharomyces cerevisiae by a SIN3-LexA fusion protein. Mol Cell Biol. 1993 Mar;13(3):1805–1814. doi: 10.1128/mcb.13.3.1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Yeung K. C., Inostroza J. A., Mermelstein F. H., Kannabiran C., Reinberg D. Structure-function analysis of the TBP-binding protein Dr1 reveals a mechanism for repression of class II gene transcription. Genes Dev. 1994 Sep 1;8(17):2097–2109. doi: 10.1101/gad.8.17.2097. [DOI] [PubMed] [Google Scholar]
  76. Zervos A. S., Gyuris J., Brent R. Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell. 1993 Jan 29;72(2):223–232. doi: 10.1016/0092-8674(93)90662-a. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES