Adenovirus E1B 19,000-molecular-weight Protein Activates C-Jun N-terminal Kinase and C-Jun-mediated Transcription

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1998 Jun 25

PMID 9632786

Citations 12

Authors

R H See

Y Shi

Affiliations

Soon will be listed here.

Abstract

Adenovirus E1B proteins (19,000-molecular-weight [19K] and 55K proteins) inhibit apoptosis and cooperate with adenovirus E1A to induce full oncogenic transformation of primary cells. The E1B 19K protein has previously been shown to be capable of activating transcription; however, the underlying mechanisms are unclear. Here, we show that adenovirus infection activates the c-Jun N-terminal kinase (JNK) and that the E1B gene products are necessary for adenovirus to activate JNK. In transfection assays, we show that the E1B 19K protein is sufficient to activate JNK and can strongly induce c-Jun-dependent transcription. Mapping studies show that the C-terminal portion of E1B 19K is necessary for induction of c-Jun-mediated transcription. Using dominant-negative mutants of several kinases upstream of JNK, we show that MEKK1 and MKK4, but not Ras, are involved in the induction of JNK activity by adenovirus infection. The same dominant-negative kinase mutants also block the ability of E1B 19K to induce c-Jun-mediated transcription. Taken together, these results suggest that E1B 19K may utilize the MEKK1-MKK4-JNK signaling pathway to activate c-Jun-dependent transcription and demonstrate a novel, kinase-activating activity of E1B 19K that may underlie its ability to regulate transcription.

Citing Articles

The role of JNK phosphorylation as a molecular target to enhance adenovirus replication, oncolysis and cancer therapeutic efficacy.

Wechman S, Rao X, Gomez-Gutierrez J, Zhou H, McMasters K Cancer Biol Ther. 2018; 19(12):1174-1184.

PMID: 30067431 PMC: 6301809. DOI: 10.1080/15384047.2018.1491503.

Combined therapy of oncolytic adenovirus and temozolomide enhances lung cancer virotherapy in vitro and in vivo.

Gomez-Gutierrez J, Nitz J, Sharma R, Wechman S, Riedinger E, Martinez-Jaramillo E Virology. 2015; 487:249-59.

PMID: 26561948 PMC: 4679495. DOI: 10.1016/j.virol.2015.10.019.

Microarray and pathway analysis reveals decreased CDC25A and increased CDC42 associated with slow growth of BCL2 overexpressing immortalized breast cell line.

Long J, Bell C, Fagg 4th W, Kushman M, Becker K, McCubrey J Cell Cycle. 2008; 7(19):3062-73.

PMID: 18838868 PMC: 2634598. DOI: 10.4161/cc.7.19.6761.

ERK- and JNK-dependent signaling pathways contribute to Bombyx mori nucleopolyhedrovirus infection.

Katsuma S, Mita K, Shimada T J Virol. 2007; 81(24):13700-9.

PMID: 17913811 PMC: 2168829. DOI: 10.1128/JVI.01683-07.

Inhibition of tumor necrosis factor (TNF) signal transduction by the adenovirus group C RID complex involves downregulation of surface levels of TNF receptor 1.

Fessler S, Chin Y, Horwitz M J Virol. 2004; 78(23):13113-21.

PMID: 15542663 PMC: 525002. DOI: 10.1128/JVI.78.23.13113-13121.2004.

References

Yee C, Baker C, Schlegel R, Howley P . Presence and expression of human papillomavirus sequences in human cervical carcinoma cell lines. Am J Pathol. 1985; 119(3):361-6. PMC: 1888002. View

Halbert D, Cutt J, Shenk T . Adenovirus early region 4 encodes functions required for efficient DNA replication, late gene expression, and host cell shutoff. J Virol. 1985; 56(1):250-7. PMC: 252513. DOI: 10.1128/JVI.56.1.250-257.1985. View

Rice S, Klessig D . Isolation and analysis of adenovirus type 5 mutants containing deletions in the gene encoding the DNA-binding protein. J Virol. 1985; 56(3):767-78. PMC: 252647. DOI: 10.1128/JVI.56.3.767-778.1985. View

Yoshida K, Venkatesh L, Kuppuswamy M, Chinnadurai G . Adenovirus transforming 19-kD T antigen has an enhancer-dependent trans-activation function and relieves enhancer repression mediated by viral and cellular genes. Genes Dev. 1987; 1(7):645-58. DOI: 10.1101/gad.1.7.645. View

Herrmann C, Mathews M . The adenovirus E1B 19-kilodalton protein stimulates gene expression by increasing DNA levels. Mol Cell Biol. 1989; 9(12):5412-23. PMC: 363709. DOI: 10.1128/mcb.9.12.5412-5423.1989. View

White E, Cipriani R . Role of adenovirus E1B proteins in transformation: altered organization of intermediate filaments in transformed cells that express the 19-kilodalton protein. Mol Cell Biol. 1990; 10(1):120-30. PMC: 360719. DOI: 10.1128/mcb.10.1.120-130.1990. View

SHIROKI K, Kato H, Kawai S . Tandemly repeated hexamer sequences within the beta interferon promoter can function as an inducible regulatory element in activation by the adenovirus E1B 19-kilodalton protein. J Virol. 1990; 64(6):3063-8. PMC: 249493. DOI: 10.1128/JVI.64.6.3063-3068.1990. View

Shi Y, Seto E, Chang L, Shenk T . Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell. 1991; 67(2):377-88. DOI: 10.1016/0092-8674(91)90189-6. View

Angel P, Karin M . The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991; 1072(2-3):129-57. DOI: 10.1016/0304-419x(91)90011-9. View

10.

Yew P, Berk A . Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. Nature. 1992; 357(6373):82-5. DOI: 10.1038/357082a0. View

11.

White E, Sabbatini P, Debbas M, Wold W, Kusher D, Gooding L . The 19-kilodalton adenovirus E1B transforming protein inhibits programmed cell death and prevents cytolysis by tumor necrosis factor alpha. Mol Cell Biol. 1992; 12(6):2570-80. PMC: 364450. DOI: 10.1128/mcb.12.6.2570-2580.1992. View

12.

Kyriakis J, App H, Zhang X, Banerjee P, Brautigan D, Rapp U . Raf-1 activates MAP kinase-kinase. Nature. 1992; 358(6385):417-21. DOI: 10.1038/358417a0. View

13.

Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S, White E . The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc Natl Acad Sci U S A. 1992; 89(16):7742-6. PMC: 49787. DOI: 10.1073/pnas.89.16.7742. View

14.

Subramanian T, Tarodi B, Govindarajan R, Boyd J, Yoshida K, Chinnadurai G . Mutational analysis of the transforming and apoptosis suppression activities of the adenovirus E1B 175R protein. Gene. 1993; 124(2):173-81. DOI: 10.1016/0378-1119(93)90391-f. View

15.

Lowe S, Ruley H . Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis. Genes Dev. 1993; 7(4):535-45. DOI: 10.1101/gad.7.4.535. View

16.

Debbas M, White E . Wild-type p53 mediates apoptosis by E1A, which is inhibited by E1B. Genes Dev. 1993; 7(4):546-54. DOI: 10.1101/gad.7.4.546. View

17.

Pleiman C, Gardner A, Blumer K, Johnson G . A divergence in the MAP kinase regulatory network defined by MEK kinase and Raf. Science. 1993; 260(5106):315-9. DOI: 10.1126/science.8385802. View

18.

Hibi M, Lin A, Smeal T, Minden A, Karin M . Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev. 1993; 7(11):2135-48. DOI: 10.1101/gad.7.11.2135. View

19.

Yew P, Liu X, Berk A . Adenovirus E1B oncoprotein tethers a transcriptional repression domain to p53. Genes Dev. 1994; 8(2):190-202. DOI: 10.1101/gad.8.2.190. View

20.

Derijard B, Hibi M, Wu I, Barrett T, Su B, Deng T . JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell. 1994; 76(6):1025-37. DOI: 10.1016/0092-8674(94)90380-8. View