Human Bcl-2 activates ERK signaling pathway to regulate activating protein-1, lens epithelium-derived growth factor and downstream genes

Hao Feng, Hua Xiang, Ying Wei Mao, Juan Wang, Jin Ping Liu, Xiao Qin Huang, Yan Liu, Shao Jun Liu, Chen Luo, Xuan Jie Zhang, Yun Liu, David Wan Cheng Li

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The proto-oncogene, bcl-2, has various functions besides its role in protecting cells from apoptosis. One of the functions is to regulate expression of other genes. Previous studies have demonstrated that Bcl-2 regulates activities of several important transcription factors including NF-κB and p53, and also their downstream genes. In our recent studies, we reported that Bcl-2 substantially downregulates expression of the endogenous αB-crystallin gene through modulating the transcriptional activity of lens epithelium-derived growth factor (LEDGF). In the present communication, we report that human Bcl-2 can positively regulate expression of the proto-oncogenes c-jun and c-fos. Moreover, it enhances the DNA binding activity and transactivity of the activating protein-1 (AP-1). Furthermore, we present evidence to show that Bcl-2 can also activate both ERK1 and ERK2 MAP kinases. Inhibition of the activities of these kinases or the upstream activating kinases by pharmacological inhibitors or dominant-negative mutants abolishes the Bcl-2-mediated regulation of AP-1, LEDGF and their downstream genes. Together, our results demonstrate that through activation of the ERK kinase signaling pathway, Bcl-2 regulates the transcriptional activities of multiple transcription factors, and hence modulates the expression of their downstream genes. Thus, our results provide a mechanism to explain how Bcl-2 may regulate expression of other genes.

Original languageEnglish (US)
Pages (from-to)7310-7321
Number of pages12
JournalOncogene
Volume23
Issue number44
DOIs
StatePublished - Sep 23 2004

Fingerprint

MAP Kinase Signaling System
Phosphotransferases
Genes
Proteins
Transcription Factors
jun Genes
Gene Expression
Crystallins
Proto-Oncogenes
Down-Regulation
Pharmacology
Apoptosis
lens epithelium-derived growth factor
DNA

Keywords

  • AP-1
  • Bcl-2
  • ERK1/2
  • LEDGF
  • Lens
  • c-fos
  • c-jun

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Human Bcl-2 activates ERK signaling pathway to regulate activating protein-1, lens epithelium-derived growth factor and downstream genes. / Feng, Hao; Xiang, Hua; Mao, Ying Wei; Wang, Juan; Liu, Jin Ping; Huang, Xiao Qin; Liu, Yan; Liu, Shao Jun; Luo, Chen; Zhang, Xuan Jie; Liu, Yun; Li, David Wan Cheng.

In: Oncogene, Vol. 23, No. 44, 23.09.2004, p. 7310-7321.

Research output: Contribution to journalArticle

Feng, H, Xiang, H, Mao, YW, Wang, J, Liu, JP, Huang, XQ, Liu, Y, Liu, SJ, Luo, C, Zhang, XJ, Liu, Y & Li, DWC 2004, 'Human Bcl-2 activates ERK signaling pathway to regulate activating protein-1, lens epithelium-derived growth factor and downstream genes', Oncogene, vol. 23, no. 44, pp. 7310-7321. https://doi.org/10.1038/sj.onc.1208041
Feng, Hao ; Xiang, Hua ; Mao, Ying Wei ; Wang, Juan ; Liu, Jin Ping ; Huang, Xiao Qin ; Liu, Yan ; Liu, Shao Jun ; Luo, Chen ; Zhang, Xuan Jie ; Liu, Yun ; Li, David Wan Cheng. / Human Bcl-2 activates ERK signaling pathway to regulate activating protein-1, lens epithelium-derived growth factor and downstream genes. In: Oncogene. 2004 ; Vol. 23, No. 44. pp. 7310-7321.
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