Enhancement of TGF-β-induced Smad3 activity by c-Abl-mediated tyrosine phosphorylation of its coactivator SKI-interacting protein (SKIP)

Kuki, Kazumasa; Yamaguchi, Noritaka; Iwasawa, Shuto; Takakura, Yuki; Aoyama, Kazumasa; Yuki, Ryuzaburo; Nakayama, Yuji; Kuga, Tetsurō; Hashimoto, Yuki; Tomonaga, Takeshi; Yamaguchi, Naoto

doi:10.1016/j.bbrc.2017.06.163

Cited by 6 publications

(5 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One likely possibility is that SNW1 undergoes posttranslational mod-ification (e.g., phosphorylation or acetylation) upon treatment with TNF-␣, which drives its transition from being a splicing factor to being a transcriptional coactivator. Recently, it was shown that SNW1 undergoes c-Abl-mediated tyrosine phosphorylation to act as a transcription coactivator for the transforming growth factor ␤ (TGF-␤) pathway (35). It would also be interesting to know the status of splicing in cells treated with TNF-␣, since we have observed that SNW1 dissociates from its splicing partners upon TNF-␣ treatment.…”

Section: Discussionmentioning

confidence: 93%

SNW1, a Novel Transcriptional Regulator of the NF-κB Pathway

Verma

Chanda

Verma

2019

Molecular and Cellular Biology

View full text Add to dashboard Cite

The nuclear factor kappa B (NF-κB) family of transcription factors plays a central role in coordinating the expression of genes that control inflammation, immune responses, cell proliferation, and a variety of other biological processes. In an attempt to identify novel regulators of this pathway, we performed whole-genome RNA interference (RNAi) screens in physiologically relevant human macrophages in response to lipopolysaccharide and tumor necrosis factor alpha (TNF-α). The top hit was SNW1, a splicing factor and transcriptional coactivator. SNW1 does not regulate the cytoplasmic components of the NF-κB pathway but complexes with the NF-κB heterodimer in the nucleus for transcriptional activation. We show that SNW1 detaches from its splicing complex (formed with SNRNP200 and SNRNP220) upon NF-κB activation and binds to NF-κB’s transcriptional elongation partner p-TEFb. We also show that SNW1 is indispensable for the transcriptional elongation of NF-κB target genes such as the interleukin 8 (IL-8) and TNF genes. SNW1 is a unique protein previously shown to be involved in both splicing and transcription, and in this case, its role involves binding to the NF-κB–p-TEFb complex to facilitate transcriptional elongation of some NF-κB target genes.

show abstract

Section: Discussionmentioning

confidence: 93%

SNW1, a Novel Transcriptional Regulator of the NF-κB Pathway

Verma

Chanda

Verma

2019

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Moreover, the phosphomimetic mutant of SKIP augmented transcriptional activity of Smad3. These results suggest that c-Abl phosphorylates SKIP mainly at Tyr292 and promotes SKIP/Smad3 interaction for the full activation of TGF-β/Smad3 signaling (45). What's more, SKIP can act on Core Binding Factor 1 (CBF1), thus inhibiting transcription in the Notch-mediated signaling pathway required for tumor growth (46).…”

Section: Foxn3 and Tgf-β Signalingmentioning

confidence: 98%

“…SKIP is an activator of Smad, in contrast to repressive Ski, competing with Ski to up-regulate the TGF-β signaling (44, 45). It has been proposed that this function of SKIP is a tumor-suppressive regulation of the TGF-β signaling pathway (45). c-Abl is a non-receptor-type tyrosine kinase that plays an important role in cell proliferation, migration, apoptosis, and fibrosis.…”

Section: Foxn3 and Tgf-β Signalingmentioning

confidence: 99%

“…c-Abl phosphorylates SKI-interacting protein (SKIP), a nuclear cofactor of the transcription factor Smad3. The c-Abl inhibitor imatinib suppressed TGF-β-induced expression of Smad3 targets as well as SKIP/Smad3 interaction (45). TGF-β-stimulation induced tyrosine phosphorylation of SKIP, and this phosphorylation was suppressed by imatinib.…”

Section: Foxn3 and Tgf-β Signalingmentioning

confidence: 99%

“…Tyr292, Tyr430, and Tyr433 residues in SKIP were shown to be involved in c-Abl-mediated phosphorylation. Phosphomimetic glutamic acid substitution at Tyr292 in SKIP enhanced, whereas its phospho-dead phenylalanine substitution attenuated TGF-β-induced SKIP/Smad3 interaction (45). Moreover, the phosphomimetic mutant of SKIP augmented transcriptional activity of Smad3.…”

Section: Foxn3 and Tgf-β Signalingmentioning

confidence: 99%

See 2 more Smart Citations

Recent Advances in Understanding FOXN3 in Breast Cancer, and Other Malignancies

et al. 2019

View full text Add to dashboard Cite

FOXN3 (forkhead box N3; CHES1: check point suppressor 1) belongs to the forkhead box (FOX) protein family. FOXN3 displays transcriptional inhibitory activity, and is involved in cell cycle regulation and tumorigenesis. FOXN3 is a tumor suppresser and alterations in FOXN3 are found in of a variety of cancers including melanoma, osteosarcoma, and hepatocellular carcinoma. While the roles of FOXN3 role in some cancers have been explored, its role in breast cancer remains unclear. Here we describe current state of knowledge of FOXN3 functions, and focus on its roles (known and potential) in breast cancer.

show abstract