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Published on: January 14, 2016
STAT3 plays an important role in DNA replication by turning on WDHD1
Yunying Zhou1,2,3, Jason J Chen4,5
1Medical Research & Laboratory Diagnostic Center, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Background:
Signal transducers and activators of transcription 3 (STAT3) is a transcription factor that plays a key role in many cellular processes such as cell growth and cancer. However, the functions and mechanisms by which STAT3 regulates cellular processes are not fully understood.
Results:
Here we describe a novel function of STAT3. We demonstrated that STAT3 plays an important role in DNA replication. Specifically, knockdown of STAT3 reduced DNA replication while activation and ectopic expression of STAT3 promoted DNA replication. We further identified the WD repeat and HMG-box DNA-binding protein 1 (WDHD1), which plays an important role in DNA replication initiation, as a novel STAT3 target gene that mediated the DNA replication function of STAT3. We showed that STAT3 bind the promoter/up regulatory region of WDHD1 gene.
Conclusions:
These studies identified a novel function of STAT3 that is mediated by its newly identified target gene WDHD1 and have important implications.
Insights
Signal transducers and activators of transcription 3 (STAT3) regulates DNA replication. STAT3 targets the WD repeat and HMG-box DNA-binding protein 1 (WDHD1) gene, revealing a novel role in cell proliferation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Signal transducers and activators of transcription 3 (STAT3) is a transcription factor involved in cell growth and cancer.
- The precise mechanisms of STAT3 in regulating cellular processes remain incompletely understood.
Purpose of the Study:
- To elucidate novel functions and regulatory mechanisms of STAT3.
- To investigate the role of STAT3 in DNA replication.
Main Methods:
- Gene knockdown and ectopic expression of STAT3.
- Analysis of DNA replication rates.
- Identification and validation of STAT3 target genes using promoter binding assays.
Main Results:
- STAT3 plays a crucial role in DNA replication; its knockdown inhibited replication, while activation promoted it.
- WD repeat and HMG-box DNA-binding protein 1 (WDHD1), a key regulator of DNA replication initiation, was identified as a novel STAT3 target gene.
- STAT3 was shown to bind the promoter/upregulatory region of the WDHD1 gene.
Conclusions:
- A novel function of STAT3 in regulating DNA replication has been identified.
- This function is mediated through its newly identified target gene, WDHD1.
- These findings have significant implications for understanding cell growth and cancer biology.
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