A WW domain-containing Yes-associated protein (YAP) is a novel transcriptional co-activator

Yagi, Ryuta; Chen, Lin Feng; Shigesada, Katsuya; Murakami, Yota; Ito, Yoshiaki

doi:10.1093/emboj/18.9.2551

Cited by 496 publications

(440 citation statements)

References 83 publications

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“…Our results suggest that interaction of RNF11 with Smurf2 allows ubiquitination of Smurf2, and this is dependent upon the presence of UbcH5a ( Figure 5). This suggests that RNF11 is required for the ubiquitination of Smurf2 that is essential to its ligase activity (Yagi et al, 1999). Interaction between UbcH5a and RNF11 was confirmed in a similar but separate experiment showing that UbcH5s, but not Ubc3, interacts with RNF11 in the absence of Smurf2 (Figure 4).…”

Section: Discussionmentioning

confidence: 62%

“…The predicted amino-acid sequence for the longest RNF11 ORF encodes a RING-H2 domain and a PY motif, both of which mediate protein -protein interactions for proteins involved in signal transduction pathways and ubiquitin (Ub)-mediated proteolysis. PY motif sequences are found in a variety of regulatory proteins including the AP-2 transcription factor, p53BP-2, RasGAP, and Smads 2, 3 and 7 (Yagi et al, 1999). Each of these proteins binds to specific WW domain containing proteins, such as YAP, WWOX, Smurf1, Smurf2 and NEDD4 (Yagi et al, 1999;Kavsak et al, 2000;Winberg et al, 2000;Conaway et al, 2002;Suzuki et al, 2002;Yendamuri et al, 2003).…”

mentioning

confidence: 99%

“…PY motif sequences are found in a variety of regulatory proteins including the AP-2 transcription factor, p53BP-2, RasGAP, and Smads 2, 3 and 7 (Yagi et al, 1999). Each of these proteins binds to specific WW domain containing proteins, such as YAP, WWOX, Smurf1, Smurf2 and NEDD4 (Yagi et al, 1999;Kavsak et al, 2000;Winberg et al, 2000;Conaway et al, 2002;Suzuki et al, 2002;Yendamuri et al, 2003). Ubiquitination-and proteasome-mediated degradation of proteins is an important step in cellular signalling, and disruption of this process has been implicated in many human diseases including cancer (Hershko and Ciechanover, 1998).…”

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confidence: 99%

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The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase

et al. 2003

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The breast cancer-associated T2A10 clone was originally isolated from a cDNA library enriched for tumour messenger ribonucleic acids. Our survey of 125 microarrayed primary tumour tissues using affinity purified polyclonal antibodies has revealed that corresponding protein is overexpressed in invasive breast cancer and is weakly expressed in kidney and prostate tumours. Now known as RNF11, the gene encodes a RING-H2 domain and a PY motif, both of which mediate protein -protein interactions. In particular, the PPPPY sequence of RNF11 PY motif is identical to that of Smad7, which has been shown to bind to WW domains of Smurf2, an E3 ubiquitin ligase that mediates the ubiquitination and degradation of the TGFb receptor complex. Using various mutants of RNF11 in GST pulldown and immunoprecipitation assays, we found that RNF11 interacts with Smurf2 through the PY motif, leading to ubiquitination of both proteins. Smurf2 plays an active role in the repression of TGFb signalling, and our data indicate that overexpression of RNF11, through its interaction with Smurf2, can restore TGFb responsiveness in transfected cells.

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Section: Discussionmentioning

confidence: 62%

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confidence: 99%

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confidence: 99%

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The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase

et al. 2003

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“…The interaction of RUNX3 and putative oncoprotein yes-associated protein (YAP) through their PY motif and WW domain, respectively, offers another perspective (Yagi et al, 1999). RUNX3's recruitment of YAP transcription co-activator results in enhanced target promoter activation.…”

Section: Runx3 Has Putative Functions In Other Cancer Signaling Pathwaysmentioning

confidence: 99%

RUNX3 is multifunctional in carcinogenesis of multiple solid tumors

2010

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The study of RUNX3 in tumor pathogenesis is a rapidly expanding area of cancer research. Functional inactivation of RUNX3-through mutation, epigenetic silencing, or cytoplasmic mislocalization-is frequently observed in solid tumors of diverse origins. This alone indicates that RUNX3 inactivation is a major risk factor in tumorigenesis and that it occurs early during progression to malignancy. Conversely, RUNX3 has also been described to have an oncogenic function in a subset of tumors. Although the mechanism of how RUNX3 switches from tumor suppressive to oncogenic activity is unclear, this is of clinical relevance with implications for cancer detection and prognosis. Recent developments have significantly contributed to our understanding of the pleiotropic tumor suppressive properties of RUNX3 that regulate major signaling pathways. This review summarizes the important findings that link RUNX3 to tumor suppression.

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“…33,34 The YAP co-activator interacts via its WW domain with a PY motif, HTYLPPPYPG, conserved in all CBF␣ family members. 35 An additional level of complexity is suggested by the ability of Cterminal segments of AML1B to inhibit CBF␤ interaction with the Runt domain. 36 Interaction with Ets-1 occurs via two AML1B segments, one near the C-terminus of the Runt domain and another centered near residue 250.…”

Section: Core Binding Factorsmentioning

confidence: 99%

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1999

Leukemia

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The AML1 and CBF␤ subunits of core binding factor (CBF) are involved in several chromosomal abnormalities frequently associated with acute leukemias. As a result, the CBF␤-SMMHC, AML1-ETO and AML1-MDS1/EVI1 fusion proteins are expressed in subsets of acute myeloid leukemia, and TEL-AML1 is expressed in B-lineage acute lymphocytic leukemia. These CBF oncoproteins likely contribute to leukemogenesis in part by inhibiting endogenous CBF. As a result they are expected to inhibit differentiation and perhaps apoptosis. In addition, the domains unique to each fusion protein may also contribute to leukemogenesis via unique mechanisms.

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A WW domain-containing Yes-associated protein (YAP) is a novel transcriptional co-activator

Cited by 496 publications

References 83 publications

The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase

The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase

RUNX3 is multifunctional in carcinogenesis of multiple solid tumors

True

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