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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
PHF6 regulates cell cycle progression by suppressing ribosomal RNA synthesis
Jiadong Wang1, Justin Wai-chung Leung, Zihua Gong
1Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
The Journal of Biological Chemistry
|December 12, 2012
Summary
PHF6 protein regulates ribosomal RNA synthesis, impacting cell proliferation and DNA stability. Its dysfunction is linked to leukemias and mental retardation, suggesting a tumor suppressor role.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Biology
Background:
- The PHF6 gene mutation causes Börjeson-Forssman-Lehmann syndrome and is found in adult T-cell acute lymphoblastic leukemias and acute myeloid leukemias.
- The in vivo function and tumor suppressor role of PHF6 remain unclear.
Purpose of the Study:
- To elucidate the in vivo function of PHF6 and its association with tumor suppression.
- To investigate the role of PHF6 in regulating ribosomal RNA (rRNA) synthesis and its impact on genomic stability.
Main Methods:
- PHF6 protein localization and interaction studies using its PHD1 domain.
- UBF (upstream binding factor) protein level analysis.
- Cell proliferation assays and cell cycle analysis (G(2)/M phase arrest).
- DNA damage assessment (phosphorylated H2AX) and analysis at the ribosomal DNA (rDNA) locus.
- RNASE1 overexpression to assess the role of RNA-DNA hybrids.
Main Results:
- PHF6 localizes to the nucleolus and is associated with ribosomal RNA promoter regions.
- PHF6 directly interacts with UBF, suppressing rRNA transcription by modulating UBF protein levels.
- PHF6 knockdown leads to impaired cell proliferation, G(2)/M phase arrest, and DNA damage accumulation at the rDNA locus.
- DNA damage in PHF6-deficient cells is linked to rRNA synthesis and can be reversed by UBF knockdown or RNASE1 overexpression.
Conclusions:
- PHF6 is a crucial regulator of rRNA synthesis.
- PHF6 plays a role in cell cycle control and genomic maintenance, particularly at the rDNA locus.
- Dysregulation of PHF6 function contributes to its putative tumor suppressor activity in leukemia.
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