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The novel secretory protein CGREF1 inhibits the activation of AP-1 transcriptional activity and cell proliferation

Weiwei Deng1, Lan Wang2, Ying Xiong3

  • 1Chinese National Human Genome Center, Beijing 100176, China; Laboratory of Medical Immunology, School of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China; Peking University Center for Human Disease Genomics, Beijing 100191, China.

The International Journal of Biochemistry & Cell Biology
|May 30, 2015
PubMed

Insights

The novel secretory protein CGREF1 inhibits the transcription factor AP-1 (activator protein-1) activity and cell proliferation. CGREF1 also suppresses ERK and p38 MAPK phosphorylation, impacting inflammation and cell survival pathways.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The transcription factor AP-1 (activator protein-1) is a key regulator involved in cellular processes such as inflammation and survival.
  • Identifying novel regulators of AP-1 activity is crucial for understanding and potentially modulating these cellular functions.

Purpose of the Study:

  • To identify novel secretory proteins that regulate the transcriptional activity of AP-1.
  • To elucidate the role of CGREF1 in AP-1 signaling, cell proliferation, and related pathways.

Main Methods:

  • A dual-luciferase reporter assay system was employed to screen a library of 940 human secretory protein cDNA clones.
  • CGREF1's secretion pathway was investigated using standard cell biology techniques.
  • The effects of CGREF1 overexpression and siRNA-mediated knockdown on AP-1 activity, MAPK phosphorylation (ERK, p38), and cell proliferation were assessed in HEK293T and HCT116 cells.

Main Results:

  • CGREF1 was identified as a secretory protein that significantly inhibits AP-1 transcriptional activity.
  • CGREF1 is secreted through the classical ER-to-Golgi pathway.
  • Overexpression of CGREF1 suppressed ERK and p38 MAPK phosphorylation and inhibited the proliferation of HEK293T and HCT116 cells.
  • Knockdown of CGREF1 using specific siRNAs led to increased AP-1 transcriptional activity.

Conclusions:

  • CGREF1 is a newly discovered secretory protein with a significant role in regulating AP-1 transcriptional activity.
  • CGREF1 influences cell proliferation by modulating MAPK signaling pathways.
  • These findings highlight CGREF1 as a potential therapeutic target for conditions involving AP-1 dysregulation.
Keywords:
AP-1CGREF1Cell proliferationMAPKSecretory protein

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