bHLH-zip transcription factor Spz1 mediates mitogen-activated protein kinase cell proliferation, transformation, and tumorigenesis

Shih Hsien Hsu, Hsiu Mei Hsieh-Li, Hsin Yi Huang, Pei Hsin Huang, Hung Li

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23 Citations (Scopus)

Abstract

BHLH-zip proteins usually play important regulatory roles in cell growth and differentiation. In this study, we show that Spz1, a bHLH-zip transcription factor, acts downstream of mitogen-activated protein kinase (MAPK, extracellular signal-regulated kinase 1/2) to up-regulate cell proliferation and tumorigenesis. In addition, through an interaction with proliferating cell nuclear antigen (PCNA) promoter, Spz1 induced cell proliferation concomitant with an increase in PCNA gene expression. Spz1-transfected cells formed colony foci on soft agar and developed fibrosarcoma tumors in nude mice. MAPK directly interacted and phosphorylated Spz1 protein, which increased PCNA transcription and cell tumorigenic activities. Reduction of endogenous Spz1 expression via RNA interference decreased cell proliferation in p19 embryonic carcinoma cells. High levels of Spz1 expression were detected in murine tumor cell lines and tumor samples of both human and Spz1 transgenic mice. Thus, Spz1 may act as a proto-oncogene, participating in the MAPK signal pathway, and be a potential therapeutic target in the treatment of Ras-induced tumors.

Original languageEnglish
Pages (from-to)4041-4050
Number of pages10
JournalCancer Research
Volume65
Issue number10
DOIs
Publication statusPublished - 2005 May 15

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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