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Regulation of Cyclin D1 RNA Stability by SNIP1
- Source :
- Cancer Research. 68:7621-7628
- Publication Year :
- 2008
- Publisher :
- American Association for Cancer Research (AACR), 2008.
-
Abstract
- Cyclin D1 expression represents one of the key mitogen-regulated events during the G1 phase of the cell cycle, whereas Cyclin D1 overexpression is frequently associated with human malignancy. Here, we describe a novel mechanism regulating Cyclin D1 levels. We find that SNIP1, previously identified as a regulator of Cyclin D1 expression, does not, as previously thought, primarily function as a transcriptional coactivator for this gene. Rather, SNIP1 plays a critical role in cotranscriptional or posttranscriptional Cyclin D1 mRNA stability. Moreover, we show that the majority of nucleoplasmic SNIP1 is present within a previously undescribed complex containing SkIP, THRAP3, BCLAF1, and Pinin, all proteins with reported roles in RNA processing and transcriptional regulation. We find that this complex, which we have termed the SNIP1/SkIP–associated RNA-processing complex, is coordinately recruited to both the 3′ end of the Cyclin D1 gene and Cyclin D1 RNA. Significantly, SNIP1 is required for the further recruitment of the RNA processing factor U2AF65 to both the Cyclin D1 gene and RNA. This study shows a novel mechanism regulating Cyclin D1 expression and offers new insight into the role of SNIP1 and associated proteins as regulators of proliferation and cancer. [Cancer Res 2008;68(18):7621–8]
- Subjects :
- Cancer Research
Cyclin E
Transcription, Genetic
Cyclin D
Cyclin A
cyclin D1
Cyclin B
Bone Neoplasms
Transfection
Polymerase Chain Reaction
Article
Cyclin D1
Cyclin-dependent kinase
Cell Line, Tumor
Humans
RNA, Messenger
RNA, Neoplasm
RNA, Small Interfering
Osteosarcoma
biology
messenger RNA
Cell Cycle
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
RNA-Binding Proteins
nucleocytoplasmic transport protein
Splicing Factor U2AF
Molecular biology
Cell biology
Gene Expression Regulation, Neoplastic
Ribonucleoproteins
Oncology
Cyclin-dependent kinase complex
biology.protein
bclaf1 protein
Cyclin A2
HeLa Cells
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....0fd0c029bb556097b98a5aa3b3496e68