Home LiteratureArticle Details
该文献已被撤稿（Retracted Publication），引用前请核实。
PMID: 2176153 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S. Retracted Publication

Cyclic-AMP-responsive transcriptional activation of CREB-327 involves interdependent phosphorylated subdomains.

The EMBO journal ·Vol. 9 ·No. 13 ·1990-12-00 ·Pages 4455-65

Lee CQ, Yun YD, Hoeffler JP, Habener JF

Abstract

Cyclic AMP-regulated gene expression is mediated by specific phosphoproteins (CREBs) which bind to cAMP-responsive elements of gene promoters. By analyzing the transactivation activities and phosphorylations in vivo of deletion and point mutated chimeric fusion proteins of the placental CREB-327, in which the DNA-binding domain is replaced by the heterologous binding-domain of the yeast transcription factor GAL4, we localized the cAMP-responsive and phosphorylated domain to a minimal-essential sequence module of 46 amino acids (residues 92-137). This serine-rich, multiply-phosphorylated sequence consists of at least three interdependent subdomains required for transcriptional activation. Although phosphorylation of serine-119 by cyclic AMP-dependent protein kinase A is necessary for transcriptional activation, such activation requires both a phosphorylated heptadecapeptide domain located ten residues amino terminal to the serine-119 and an eleven-residue domain carboxyl terminal to the serine-119. Deletion of these two domains does not impair phosphorylation of serine-119. Further, deletion of the carboxyl-terminal domain does not alter phosphorylation of the heptadecapeptide domain. We propose that akin to the phosphorylation-dependent activation of enzymes, the transcriptional transactivation functions of CREB-327 involve a phosphorylation-dependent allosteric conformational mechanism.

MeSH Terms
Amino Acid Sequence Binding Sites Cyclic AMP/pharmacology Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins/biosynthesis,genetics Humans Molecular Sequence Data Mutation Phosphorylation Protein Kinases/metabolism Serine/metabolism Transcription Factors/genetics Transcription, Genetic Transcriptional Activation/drug effects Tumor Cells, Cultured
Chemicals
Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins Transcription Factors Serine Cyclic AMP Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lee C Q
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston.
Yun Y D
Hoeffler J P
Habener J F
References (59)
59 references, click to expand
  1. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  2. GAL4-VP16 is an unusually potent transcriptional activator.
    Nature. 1988 Oct 6;335(6190):563-4 PMID: 3047590
  3. How eukaryotic transcriptional activators work.
    Nature. 1988 Oct 20;335(6192):683-9 PMID: 3050531
  4. Phosphorylation of the rev gene product of human immunodeficiency virus type 1.
    J Virol. 1988 Dec;62(12):4801-4 PMID: 2846891
  5. The catalytic subunit of cAMP-dependent protein kinase induces expression of genes containing cAMP-responsive enhancer elements.
    Nature. 1988 Nov 3;336(6194):83-6 PMID: 2847055
  6. Cyclic AMP and phorbol ester-stimulated transcription mediated by similar DNA elements that bind distinct proteins.
    Proc Natl Acad Sci U S A. 1988 Nov;85(21):7922-6 PMID: 2847147
  7. Structural determinants for transcriptional activation by cAMP-responsive DNA elements.
    J Biol Chem. 1988 Dec 5;263(34):18466-72 PMID: 2848037
  8. Structural and functional characterization of human immunodeficiency virus tat protein.
    J Virol. 1989 Jan;63(1):1-8 PMID: 2535718
  9. Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA.
    Science. 1988 Dec 9;242(4884):1430-3 PMID: 2974179
  10. A family of immunologically related transcription factors that includes multiple forms of ATF and AP-1.
    Genes Dev. 1988 Oct;2(10):1216-26 PMID: 3144478
  11. A cluster of phosphorylation sites on the cyclic AMP-regulated nuclear factor CREB predicted by its sequence.
    Nature. 1989 Feb 23;337(6209):749-52 PMID: 2521922
  12. Both isoforms of the cAMP-dependent protein kinase catalytic subunit can activate transcription of the prolactin gene.
    J Biol Chem. 1989 Apr 25;264(12):6870-3 PMID: 2540166
  13. Regulation of transcription by cyclic AMP-dependent protein kinase.
    Proc Natl Acad Sci U S A. 1989 Jul;86(13):4887-91 PMID: 2544878
  14. Myc oncoproteins are phosphorylated by casein kinase II.
    EMBO J. 1989 Apr;8(4):1111-9 PMID: 2663470
  15. Distinct adenosine 3',5'-monophosphate and phorbol ester-responsive signal transduction pathways converge at the level of transcriptional activation by the interactions of DNA-binding proteins.
    Mol Endocrinol. 1989 May;3(5):868-80 PMID: 2547158
  16. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain.
    Cell. 1989 Aug 25;58(4):741-53 PMID: 2504497
  17. Two tobacco DNA-binding proteins with homology to the nuclear factor CREB.
    Nature. 1989 Aug 31;340(6236):727-30 PMID: 2528073
  18. A protein that binds to a cis-acting element of wheat histone genes has a leucine zipper motif.
    Science. 1989 Sep 1;245(4921):965-7 PMID: 2772648
  19. Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain.
    EMBO J. 1989 Jul;8(7):2023-8 PMID: 2529117
  20. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133.
    Cell. 1989 Nov 17;59(4):675-80 PMID: 2573431
  21. Plasmids encoding PKI(1-31), a specific inhibitor of cAMP-stimulated gene expression, inhibit the basal transcriptional activity of some but not all cAMP-regulated DNA response elements in JEG-3 cells.
    J Biol Chem. 1989 Nov 25;264(33):19506-13 PMID: 2479635
  22. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1.
    Cell. 1989 Dec 1;59(5):827-36 PMID: 2512012
  23. Both the basic region and the 'leucine zipper' domain of the cyclic AMP response element binding (CREB) protein are essential for transcriptional activation.
    EMBO J. 1990 Jan;9(1):225-32 PMID: 2136830
  24. Stimulation of casein kinase II by epidermal growth factor: relationship between the physiological activity of the kinase and the phosphorylation state of its beta subunit.
    Proc Natl Acad Sci U S A. 1990 Jan;87(2):821-5 PMID: 2300566
  25. Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation.
    Cell. 1990 Feb 9;60(3):375-86 PMID: 2302733
  26. Characterization of a bipartite activator domain in transcription factor CREB.
    Cell. 1990 Feb 23;60(4):611-7 PMID: 2137373
  27. Glycogen phosphorylase. The structural basis of the allosteric response and comparison with other allosteric proteins.
    J Biol Chem. 1990 Feb 15;265(5):2409-12 PMID: 2137445
  28. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers.
    Genes Dev. 1989 Dec;3(12B):2083-90 PMID: 2516827
  29. Two distinct forms of active transcription factor CREB (cAMP response element binding protein).
    Proc Natl Acad Sci U S A. 1990 Jul;87(14):5258-62 PMID: 2142528
  30. Multiple adenosine 3',5'-cyclic [corrected] monophosphate response element DNA-binding proteins generated by gene diversification and alternative exon splicing.
    Mol Endocrinol. 1990 Jun;4(6):920-30 PMID: 2146494
  31. DNA-binding and dimerization domains of adenosine 3',5'- cyclic monophosphate-responsive protein CREB reside in the carboxyl-terminal 66 amino acids.
    Mol Endocrinol. 1990 Jun;4(6):931-9 PMID: 2146495
  32. The E7 protein of human papillomavirus type 16 is phosphorylated by casein kinase II.
    New Biol. 1989 Oct;1(1):44-53 PMID: 2562189
  33. Casein kinases--multipotential protein kinases.
    Curr Top Cell Regul. 1982;21:101-27 PMID: 6814825
  34. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells.
    Mol Cell Biol. 1982 Sep;2(9):1044-51 PMID: 6960240
  35. Amino terminus of the yeast GAL4 gene product is sufficient for nuclear localization.
    Proc Natl Acad Sci U S A. 1984 Oct;81(19):5951-5 PMID: 6091123
  36. Synthetic peptides including acidic clusters as substrates and inhibitors of rat liver casein kinase TS (type-2).
    J Biol Chem. 1984 Dec 10;259(23):14576-9 PMID: 6594339
  37. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma.
    Cell. 1984 Dec;39(3 Pt 2):653-62 PMID: 6096017
  38. A synthetic peptide substrate specific for casein kinase II.
    Proc Natl Acad Sci U S A. 1985 Feb;82(3):737-41 PMID: 2983313
  39. A potent synthetic peptide inhibitor of the cAMP-dependent protein kinase.
    J Biol Chem. 1986 Jan 25;261(3):989-92 PMID: 3511044
  40. Separation of DNA binding from the transcription-activating function of a eukaryotic regulatory protein.
    Science. 1986 Feb 14;231(4739):699-704 PMID: 3080805
  41. Sequence analysis of phosphoserine-containing peptides. Modification for picomolar sensitivity.
    FEBS Lett. 1986 Aug 11;204(1):61-6 PMID: 3091399
  42. Deletion analysis of GAL4 defines two transcriptional activating segments.
    Cell. 1987 Mar 13;48(5):847-53 PMID: 3028647
  43. Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene.
    Nature. 1987 Jul 9-15;328(6126):175-8 PMID: 2885756
  44. Cyclic AMP responsiveness of human gonadotropin-alpha gene transcription is directed by a repeated 18-base pair enhancer. Alpha-promoter receptivity to the enhancer confers cell-preferential expression.
    J Biol Chem. 1987 Sep 5;262(25):12169-74 PMID: 3040732
  45. Mutants of GAL4 protein altered in an activation function.
    Cell. 1987 Oct 9;51(1):121-6 PMID: 3115592
  46. trans-acting factors interact with a cyclic AMP response element to modulate expression of the human gonadotropin alpha gene.
    Mol Cell Biol. 1987 Sep;7(9):3032-40 PMID: 2823116
  47. Transcription in yeast activated by a putative amphipathic alpha helix linked to a DNA binding unit.
    Nature. 1987 Dec 17-23;330(6149):670-2 PMID: 3317067
  48. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 PMID: 388439
  49. Transcription factor ATF interacts with the TATA factor to facilitate establishment of a preinitiation complex.
    Cell. 1988 Sep 23;54(7):1033-42 PMID: 3416354
  50. Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis.
    J Biol Chem. 1977 Feb 10;252(3):1102-6 PMID: 320200
  51. GAL4 activates gene expression in mammalian cells.
    Cell. 1988 Jan 29;52(2):161-7 PMID: 2830021
  52. The yeast UASG is a transcriptional enhancer in human HeLa cells in the presence of the GAL4 trans-activator.
    Cell. 1988 Jan 29;52(2):169-78 PMID: 2830022
  53. Transcriptional activation. Acid blobs and negative noodles.
    Nature. 1988 May 19;333(6170):210-2 PMID: 3367995
  54. Interaction of a common cellular transcription factor, ATF, with regulatory elements in both E1a- and cyclic AMP-inducible promoters.
    Proc Natl Acad Sci U S A. 1988 May;85(10):3396-400 PMID: 2835770
  55. Structural and functional characterization of the short acidic transcriptional activation region of yeast GCN4 protein.
    Nature. 1988 Jun 16;333(6174):635-40 PMID: 3287180
  56. Cyclic AMP and the induction of eukaryotic gene transcription.
    J Biol Chem. 1988 Jul 5;263(19):9063-6 PMID: 2837474
  57. The gonadotropin alpha-gene contains multiple protein binding domains that interact to modulate basal and cAMP-responsive transcription.
    J Biol Chem. 1988 Jul 15;263(20):9879-86 PMID: 2454922
  58. Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB.
    Nature. 1988 Aug 11;334(6182):494-8 PMID: 2900470
  59. Mechanism of action of a yeast activator: direct effect of GAL4 derivatives on mammalian TFIID-promoter interactions.
    Cell. 1988 Aug 26;54(5):665-9 PMID: 3044608
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1990-12-00
Pages
4455-65
Language
English
Region
England
NLM ID
8208664
PMCID
PMC552238
Subset
IM
Grants
NIDDK NIH HHS · DK25532 · United States
NIDDK NIH HHS · DK30457 · United States
Corrections
RetractionIn
PMID: 8013471
CommentIn
PMID: 8615993
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2