Regulation of Cyclin D1 RNA Stability by SNIP1

Bracken, Cameron P.; Wall, Stephen; Barré, Benjamin; Panov, Kostya I.; Ajuh, Paul; Perkins, Neil D.

doi:10.1158/0008-5472.can-08-1217

Cited by 89 publications

(89 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…35 Recently, Bclaf1 was identified as a component of the RNA splicing complex and regulates the stability of cyclin D and BRCA1 mRNA. 36,37 Whether this function of Bclaf1 is related to C/EBPβ upregulation requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Bclaf1 is an important NF-κB signaling transducer and C/EBPβ regulator in DNA damage-induced senescence

Sun

Geng

et al. 2016

Cell Death Differ

View full text Add to dashboard Cite

Inducing senescence in cancer cells is an effective approach to suppress cancer growth, and it contributes significantly to the efficacy of therapeutic drugs. Previous studies indicated that transcription factors NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) and C/EBPβ (CCAAT/enhancer-binding protein-β) play a critical role in the establishment of senescence by upregulating proinflammatory cytokines, notably interleukin-6 (IL-6) and interleukin-8 (IL-8). However, it is not clear how these two factors are activated in response to senescence-inducing stimuli and subsequently regulate gene transcription. Here, we reveal Bcl-2-associated transcription factor 1 (Bclaf1) as a novel player in the therapeutic drug doxorubicin-induced senescence (TIS) in multiple cancer cells. Bclaf1 is upregulated through the ATM/Nemo/NF-κB pathway during TIS and is a direct target of p65 and c-Rel. The induction of Bclaf1 by NF-κB is essential for C/EBPβ upregulation and IL-6/IL-8 transcription during TIS. Bclaf1 can interact with the leucine zipper region of C/EBPβ and cooperate with C/EBPβ to upregulate IL-8. Furthermore, we show that Bclaf1 is required for the effectiveness of doxorubicin (Dox) treatment-induced tumor suppression in a xenograft tumor model. These finding suggest that Bclaf1 plays a crucial role in transducing the senescence-inducing signal from NF-κB to C/EBPβ during TIS, thus amplifying the signals for the establishment of senescence. Given the recent revelation that Bclaf1 is involved in tumorigenesis, our data indicate that the responsiveness of Bclaf1 to NF-κB may determine the effectiveness of therapeutic drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Bclaf1 is an important NF-κB signaling transducer and C/EBPβ regulator in DNA damage-induced senescence

Sun

Geng

et al. 2016

Cell Death Differ

View full text Add to dashboard Cite

show abstract

“…However, the role in apoptotic pathway remains controversial, as cells from BCLAF1-deficient mice do not have obvious defects in apoptosis 2 . Indeed, multiple functions have been described for BCLAF1 by different groups, such as in posttranscriptional processes 3,4 , production of Kaposi's sarcoma-associated herpesvirus 5 and human cytomegalovirus infection 6 , lung development and T-cell activation 2,7 .…”

mentioning

confidence: 99%

BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells

et al. 2014

View full text Add to dashboard Cite

Bcl-2-associated transcription factor 1 (BCLAF1) is known to be involved in multiple biological processes. Although several splice variants of BCLAF1 have been identified, little is known about how BCLAF1 splicing is regulated or the contribution of alternative splicing to its developmental functions. Here we find that inclusion of alternative exon5a was significantly increased in colorectal cancer (CRC) samples. Knockdown of the BCLAF1 protein isoform resulting from exon5a inclusion inhibited growth and that its overexpression increased tumorigenic potential. We also found that the splicing factor SRSF10 stimulates inclusion of exon5a and has growth-inducing activity. Importantly, the upregulation of SRSF10 expression observed in clinical CRC samples parallels the increased inclusion of BCLAF1 exon5a, both of which are associated with higher tumour grade. These findings identify SRSF10 as a key regulator of BCLAF1 pre-mRNA splicing and the maintenance of oncogenic features in human colon cancer cells.

show abstract

“…This protein is also an acetyltransferase and its phosphorylation, regulated by Tyr-490, could contribute to the regulation of transcription through remodeling histone modifications along with CHD3 and TRIM28 cited above. The complex SNARP (SNIP1/SkIPassociated RNA processing) contains THRAP3 (thyroid hormone receptor-associated protein 3) and BCLAF (Bcl-2-associated transcription factor 1), whose phosphorylations were both found to be regulated by Tyr-490 and has been reported as targeting cyclin D1 RNA processing (26). These two proteins are also coactivators of a nuclear receptor and its transcriptional activity (THRAP3 (27)) and a repressor of transcriptional activity (BCLAF (28)).…”

Section: Discussionmentioning

confidence: 99%

Dissecting the Roles of Tyrosines 490 and 785 of TrkA Protein in the Induction of Downstream Protein Phosphorylation Using Chimeric Receptors

Biarc

Chalkley

Burlingame

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Receptor tyrosine kinases generally act by forming phosphotyrosine-docking sites on their own endodomains that propagate signals through cascades of post-translational modifications driven by the binding of adaptor/effector proteins. The pathways that are stimulated in any given receptor tyrosine kinase are a function of the initial docking sites that are activated and the availability of downstream participants. In the case of the Trk receptors, which are activated by nerve growth factor, there are only two established phosphotyrosine-docking sites (Tyr-490 and Tyr-785 on TrkA) that are known to be directly involved in signal transduction. Taking advantage of this limited repertoire of docking sites and the availability of PC12 cell lines stably transfected with chimeric receptors composed of the extracellular domain of the PDGF receptor and the transmembrane and intracellular domains of TrkA, the downstream TrkA-induced phosphoproteome was assessed for the “native” receptor and mutants lacking Tyr-490 or both Tyr-490 and Tyr-785. Basal phosphorylation levels were compared with those formed after 20 min of stimulation with PDGF. Several thousand phosphopeptides were identified after TiO2 enrichment, and many were up- or down-regulated by receptor activation. The modified proteins in the native sample contained many of the well established participants in TrkA signaling. The results from the mutant receptors allowed grouping of these downstream targets by their dependence on the two characterized docking site(s). A clear subset that was not dependent on either Tyr-490 or Tyr-785 emerged, providing direct evidence that there are other sites on TrkA that are involved in downstream signaling.

show abstract

Regulation of Cyclin D1 RNA Stability by SNIP1

Cited by 89 publications

References 35 publications

Bclaf1 is an important NF-κB signaling transducer and C/EBPβ regulator in DNA damage-induced senescence

Bclaf1 is an important NF-κB signaling transducer and C/EBPβ regulator in DNA damage-induced senescence

BCLAF1 and its splicing regulator SRSF10 regulate the tumorigenic potential of colon cancer cells

Dissecting the Roles of Tyrosines 490 and 785 of TrkA Protein in the Induction of Downstream Protein Phosphorylation Using Chimeric Receptors

Contact Info

Product

Resources

About