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Published on: December 7, 2017
Tip60 modulates PLAGL2-mediated transactivation by acetylation
Jinying Ning1, Gang Zheng, Yu-Chung Yang
1Department of Pharmacology and Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Journal of Cellular Biochemistry
|June 7, 2007
Summary
Tip60 protein acetylates and inhibits sumoylation of Pleiomorphic adenoma gene-like 2 (PLAGL2), a key oncogene. This acetylation enhances PLAGL2
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Pleiomorphic adenoma gene (PLAG) family proteins, including PLAGL2, are oncogenes implicated in various cancers.
- Overexpression of PLAGL2 drives cell transformation and proliferation, but its regulatory mechanisms remain unclear.
- Previous studies indicated that sumoylation negatively regulates PLAGL2 transcriptional activity.
Purpose of the Study:
- To investigate the role of Tip60 in modulating PLAGL2 function.
- To elucidate the mechanism by which Tip60 regulates PLAGL2 activity.
- To determine if Tip60 acts as a coactivator for PLAGL2.
Main Methods:
- Assessing the interaction between Tip60 and PLAGL2 using its zinc finger domain.
- Evaluating the effect of wild-type and HAT-mutant Tip60 on PLAGL2-mediated transactivation.
- Analyzing the impact of Tip60 coexpression on PLAGL2 sumoylation.
- Investigating the influence of Tip60 and DN-Ubc9 on wild-type versus sumoylation-deficient PLAGL2.
Main Results:
- Tip60 directly associates with and acetylates PLAGL2.
- Histone acetyltransferase (HAT)-active Tip60 enhances PLAGL2 transactivation, while the HAT-minus mutant does not.
- Coexpression of Tip60 with PLAGL2 completely abolishes PLAGL2 sumoylation.
- Tip60 and DN-Ubc9 increase wild-type PLAGL2 activity but not the sumoylation-deficient mutant (K250, 269, 356R).
- Tip60's effects on PLAGL2 target gene promoters are promoter-specific.
Conclusions:
- Tip60 acts as a novel, promoter-specific coactivator of PLAGL2.
- Tip60 inhibits PLAGL2 sumoylation, potentially by acetylating the same lysine residues targeted by sumoylation.
- This study reveals Tip60's function as a sumoylation inhibitor through its acetyltransferase activity, regulating specific gene expression.
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