SKI and MEL1 Cooperate to Inhibit Transforming Growth Factor-β Signal in Gastric Cancer Cells

Takahata, Mami; Inoue, Yasumichi; Tsuda, Hitoshi; Imoto, Issei; Koinuma, Daizo; Hayashi, Makoto; Ichikura, Takashi; Yamori, Takao; Nagasaki, Koichi; Yoshida, Mika; Matsuoka, Masao; Morishita, Kazuhiro; Yuki, Keiko; Hanyu, Aki; Miyazawa, Keiji; Inazawa, Johji; Miyazono, Kohei; Imamura, Takeshi

doi:10.1074/jbc.m808989200

Cited by 80 publications

(77 citation statements)

References 45 publications

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“…At the transcriptional level, this is best illustrated by EGL-43-and Hamlet-mediated regulation of Notch in invertebrates (Endo et al, 2012;Hwang et al, 2007;Rimann and Hajnal, 2007), and by Prdm3-and Prdm16-mediated regulation of Smad activity in vertebrates (Alliston et al, 2005;Bjork et al, 2010;Izutsu et al, 2001;Sato et al, 2008;Takahata et al, 2009). Because Prdm factors can create global changes in chromatin state, they have interesting potential to construct cell-type-specific chromatin contexts upon which developmental signalling pathways can operate.…”

Section: Discussionmentioning

confidence: 99%

“…Development 139 (13) G9a (Gyory et al, 2004), Lsd1 ), Hdac2 (Yu et al, 2000), Prmt5 (Ancelin et al, 2006) Groucho family (Tle1 and Tle2) (Ren et al, 1999) and Irf4 (Gupta et al, 2001) Prdm2 H3K9 methlytransferase (Kim et al, 2003) p300 (Carling et al, 2004) Prdm2 homodimer (Huang et al, 1998), Rb1 (Buyse et al, 1995) and ER (Medici et al, 1999) Prdm3 p300 (Chakraborty et al, 2001), P/CAF, HDACs (Alliston et al, 2005), SuV39H1 (Cattaneo and Nucifora, 2008), Dnmt3a/b (Senyuk et al, 2011), Mbd3 (Spensberger et al, 2008), Uxt (McGilvray et al, 2007) and PRC (Yoshimi et al, 2011) CtBP (Izutsu et al, 2001;Palmer et al, 2001), Gata1 (Laricchia-Robbio et al, 2006), Jnk (Kurokawa et al, 2000;Spensberger et al, 2008), Runx1 (Senyuk et al, 2007), Smad1/2 (Alliston et al, 2005), Smad3 (Kurokawa et al, 1998) HDACs and p300 (Takahata et al, 2009) Ppar /Ppar , SKI (Takahata et al, 2009), Smad3 (Warner et al, 2007), CtBP , C/EBP ) and Ppargc1 /Ppargc1 (Seale et al, 2007) Bhlhb5, basic helix-loop-helix domain-containing class B5; C/EBP , (CCAAT/enhancer-binding protein ); CtBP, C-terminal binding protein; Dnmt, DNA methyltransferase; ER, oestrogen receptor; Gfi1, growth factor independent 1; HDAC, histone deacetylases; Irf4, interferon regulatory factor 4; Jnk, c-Jun N-terminal kinase; Lsd1, lysinespecific demethylase 1; Mbd3, methyl-CpG binding domain protein 3; Pu.1, SFFV proviral integration 1; P/CAF, p300/CBP-associated factor; Ppar, peroxisomeproliferator-activated receptor; Ppargc1, Ppar co-activator 1 ; Prc, Polycomb repressive complex; Prmt5, protein methyltransferase 5; Rb1, retinoblastoma 1; Runx1, runt-related transcription factor; Smad, MAD homologue; Tle, transducin-like enhancer of split; Uxt, ubiquitously transcribed tetratricopeptide r...…”

Section: Reviewmentioning

confidence: 99%

“…EGL-43 in C. elegans and Hamlet in Drosophila are linked to the Notch pathway (Endo et al, 2012;Hwang et al, 2007;Moore et al, 2004;Rimann and Hajnal, 2007), and Prdm3 and Prdm16 to TGF (Alliston et al, 2005;Bjork et al, 2010;Sato et al, 2008;Takahata et al, 2009). Bi-directional transcription regulation activity of Prdm2 at the pS2 promoter provides one solution of how to amplify the outcome of signalling at a specific target promoter (Carling et al, 2004).…”

Section: Effects Of Prdms On Oestrogen Signallingmentioning

confidence: 99%

“…that Prdm3 and Prdm16 bind Smads in order to repress Smadmediated transcriptional activation (Alliston et al, 2005;Bjork et al, 2010;Sato et al, 2008;Takahata et al, 2009). This Prdmmediated TGF repression requires recruitment of CtBP, which in turn recruits HDACs to deacetylate histones at Smad target promoters (Alliston et al, 2005;Izutsu et al, 2001).…”

Section: Modulation Of Tgf Signallingmentioning

confidence: 99%

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The Prdm family: expanding roles in stem cells and development

2012

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SummaryMembers of the Prdm family are characterized by an Nterminal PR domain that is related to the SET methyltransferase domain, and multiple zinc fingers that mediate sequence-specific DNA binding and protein-protein interactions. Prdm factors either act as direct histone methyltransferases or recruit a suite of histone-modifying enzymes to target promoters. In this way, they function in many developmental contexts to drive and maintain cell state transitions and to modify the activity of developmental signalling pathways. Here, we provide an overview of the structure and function of Prdm family members and discuss the roles played by these proteins in stem cells and throughout development.

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Section: Discussionmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Section: Effects Of Prdms On Oestrogen Signallingmentioning

confidence: 99%

Section: Modulation Of Tgf Signallingmentioning

confidence: 99%

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The Prdm family: expanding roles in stem cells and development

2012

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“…Furthermore, the TGF-␤ inhibitory proteins SKI and SKIL are present in SMAD2/3/4 affinity purifications. These two proteins are known direct interactors of the SMAD2/3/4 complex (19,20). In addition and as expected, we identified the R-SMAD inhibitor LEMD3 (MAN1) (21,22) as a SMAD3 interactor.…”

Section: Gfp-smad Cell Linementioning

confidence: 74%

Quantitative Proteomics of the SMAD (Suppressor of Mothers against Decapentaplegic) Transcription Factor Family Identifies Importin 5 as a Bone Morphogenic Protein Receptor SMAD-specific Importin

Baas

Sijm

Teeffelen

et al. 2016

Journal of Biological Chemistry

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Edited by Xiao-Fan WangGene-specific transcription factors (GSTFs) control gene transcription by DNA binding and specific protein complex recruitment, which regulates promoter accessibility for transcription initiation by RNA polymerase II. Mutations in the GSTFs Suppressor of Mothers Against Decapentaplegic 2 (SMAD2) and SMAD4 are frequently associated with colon and rectal carcinomas. These proteins play an important role in bone morphogenic protein (BMP) and transforming growth factor ␤ (TGF-␤) signaling pathways controlling cell fate and proliferation. To study the protein interactome of the SMAD protein family we generated a quantitative proteomics pipeline that allows for inducible expression of GFP-tagged SMAD proteins followed by affinity purification and quantitative mass spectrometry analysis. Data are available via ProteomeXchange with identifier PXD004529. The nuclear importin IPO5 was identified as a novel interacting protein of SMAD1. Overexpression of IPO5 in various cell lines specifically increases nuclear localization of BMP receptor-activated SMADs (R-SMADs) confirming a functional relationship between IPO5 and BMP but not TGF-␤ R-SMADs. Finally, we provide evidence that variation in length of the lysine stretch of the nuclear localization sequence is a determinant for importin specificity.Transcription regulation is a tightly controlled process that is influenced by the binding of gene-specific transcription factors (GSTFs) 2 to specific DNA elements (1). These GSTF families are highly heterogeneous, spanning several hundreds of proteins like the C 2 H 2 -type zinc fingers (2) to the eight members of the SMAD protein family. Binding of GSTFs to DNA elements mediates recruitment of multisubunit co-activator complexes like SET/MLL, Mediator, TFIID, or the BAF remodeler, each of which can specifically affect the chromatin microenvironment resulting in alteration of gene transcriptional states. Cancer genome-wide association studies have shown that GSTFs and chromatin-associated proteins are often mutated in various solid tumors types (3-5). In particular, mutations in SMAD2 and SMAD4 have been frequently associated with colon and rectal carcinomas (5.7 and 9.8%, respectively) (3). The eight SMAD family members can be divided into the R-SMADs (SMAD1/2/3/5/9), I-SMADs (SMAD6/7), and Co-SMAD (SMAD4) (Fig. 1A). R-SMADs can additionally be subdivided into BMP (SMAD1/5/9) and TGF-␤ (SMAD2/3) subclasses depending on the ligand activating.SMAD signaling starts with the activation of the anaplastic lymphoma kinase type II receptors by the binding of the BMP or TGF-␤ cytokines. Activation of type II receptors recruits and phosphorylates anaplastic lymphoma kinase type I receptors, which in turn activate the R-SMADs by phosphorylating the SSXS residues in the C-terminal domain (6 -8). In basal conditions the SMADs shuttle constantly between the cytoplasm and the nucleus (9) via interaction with the nucleoporins (10). After receptor-mediated R-SMAD activation, an import protein is required for their nuclear...

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PRDM proteins: Important players in differentiation and disease

2011

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The PRDM family has recently spawned considerable interest as it has been implicated in fundamental aspects of cellular differentiation and exhibits expanding ties to human diseases. The PRDMs belong to the SET domain family of histone methyltransferases, however, enzymatic activity has been determined for only few PRDMs suggesting that they act by recruiting co-factors or, more speculatively, confer methylation of non-histone targets. Several PRDM family members are deregulated in human diseases, most prominently in hematological malignancies and solid cancers, where they can act as both tumor suppressors or drivers of oncogenic processes. The molecular mechanisms have been delineated for only few PRDMs and little is known about functional redundancy within the family. Future studies should identify target genes of PRDM proteins and the protein complexes in which PRDM proteins reside to provide a more comprehensive understanding of the biological and biochemical functions of this important protein family.

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SKI and MEL1 Cooperate to Inhibit Transforming Growth Factor-β Signal in Gastric Cancer Cells

Cited by 80 publications

References 45 publications

The Prdm family: expanding roles in stem cells and development

The Prdm family: expanding roles in stem cells and development

Quantitative Proteomics of the SMAD (Suppressor of Mothers against Decapentaplegic) Transcription Factor Family Identifies Importin 5 as a Bone Morphogenic Protein Receptor SMAD-specific Importin

PRDM proteins: Important players in differentiation and disease

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