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000292155 041__ $$aEnglish
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000292155 1001_ $$aWesener, Marie C$$b0
000292155 245__ $$aCRKL Enhances YAP Signaling through Binding and JNK/JUN Pathway Activation in Liver Cancer.
000292155 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2024
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000292155 520__ $$aThe Hippo pathway transducers yes-associated protein (YAP) and WW-domain containing transcription regulator 1 (WWTR1/TAZ) are key regulators of liver tumorigenesis, promoting tumor formation and progression. Although the first inhibitors are in clinical trials, targeting the relevant upstream regulators of YAP/TAZ activity could prove equally beneficial. To identify regulators of YAP/TAZ activity in hepatocarcinoma (HCC) cells, we carried out a proximity labelling approach (BioID) coupled with mass spectrometry. We verified CRK-like proto-oncogene adaptor protein (CRKL) as a new YAP-exclusive interaction partner. CRKL is highly expressed in HCC patients, and its expression is associated with YAP activity as well as poor survival prognosis. In vitro experiments demonstrated CRKL-dependent cell survival and the loss of YAP binding induced through actin disruption. Moreover, we delineated the activation of the JNK/JUN pathway by CRKL, which promoted YAP transcription. Our data illustrate that CRKL not only promoted YAP activity through its binding but also through the induction of YAP transcription by JNK/JUN activation. This emphasizes the potential use of targeting the JNK/JUN pathway to suppress YAP expression in HCC patients.
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000292155 650_7 $$2Other$$aAP1
000292155 650_7 $$2Other$$aBioID
000292155 650_7 $$2Other$$aCRK
000292155 650_7 $$2Other$$aHCC
000292155 650_7 $$2Other$$aHippo
000292155 650_7 $$2Other$$aMS
000292155 650_7 $$2Other$$aTEAD
000292155 650_7 $$2Other$$ac-Jun
000292155 650_7 $$2Other$$aproteomics
000292155 650_7 $$2Other$$asurvival
000292155 650_7 $$2NLM Chemicals$$aAdaptor Proteins, Signal Transducing
000292155 650_7 $$2NLM Chemicals$$aTranscription Factors
000292155 650_7 $$2NLM Chemicals$$aCRKL protein
000292155 650_7 $$2NLM Chemicals$$aYAP-Signaling Proteins
000292155 650_7 $$2NLM Chemicals$$aMAS1 protein, human
000292155 650_7 $$2NLM Chemicals$$aYAP1 protein, human
000292155 650_7 $$2NLM Chemicals$$aNuclear Proteins
000292155 650_7 $$2NLM Chemicals$$aProto-Oncogene Mas
000292155 650_2 $$2MeSH$$aHumans
000292155 650_2 $$2MeSH$$aLiver Neoplasms: metabolism
000292155 650_2 $$2MeSH$$aLiver Neoplasms: pathology
000292155 650_2 $$2MeSH$$aLiver Neoplasms: genetics
000292155 650_2 $$2MeSH$$aAdaptor Proteins, Signal Transducing: metabolism
000292155 650_2 $$2MeSH$$aAdaptor Proteins, Signal Transducing: genetics
000292155 650_2 $$2MeSH$$aTranscription Factors: metabolism
000292155 650_2 $$2MeSH$$aTranscription Factors: genetics
000292155 650_2 $$2MeSH$$aYAP-Signaling Proteins: metabolism
000292155 650_2 $$2MeSH$$aCarcinoma, Hepatocellular: metabolism
000292155 650_2 $$2MeSH$$aCarcinoma, Hepatocellular: pathology
000292155 650_2 $$2MeSH$$aCarcinoma, Hepatocellular: genetics
000292155 650_2 $$2MeSH$$aNuclear Proteins: metabolism
000292155 650_2 $$2MeSH$$aNuclear Proteins: genetics
000292155 650_2 $$2MeSH$$aProto-Oncogene Mas
000292155 650_2 $$2MeSH$$aCell Line, Tumor
000292155 650_2 $$2MeSH$$aProtein Binding
000292155 650_2 $$2MeSH$$aMAP Kinase Signaling System
000292155 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic
000292155 650_2 $$2MeSH$$aSignal Transduction
000292155 7001_ $$aWeiler, Sofia M E$$b1
000292155 7001_ $$aBissinger, Michaela$$b2
000292155 7001_ $$aKlessinger, Tobias F$$b3
000292155 7001_ $$aRose, Fabian$$b4
000292155 7001_ $$00009-0000-4052-9927$$aMerker, Sabine$$b5
000292155 7001_ $$aLuzarowski, Marcin$$b6
000292155 7001_ $$aRuppert, Thomas$$b7
000292155 7001_ $$0P:(DE-He78)1c49e2bc4134e93b5dc7d9845e30c039$$aHelm, Barbara$$b8$$udkfz
000292155 7001_ $$0P:(DE-He78)860df4ab16c373fb28a815dcd81107a6$$aKlingmüller, Ursula$$b9$$udkfz
000292155 7001_ $$aSchirmacher, Peter$$b10
000292155 7001_ $$aBreuhahn, Kai$$b11
000292155 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms25158549$$gVol. 25, no. 15, p. 8549 -$$n15$$p8549$$tInternational journal of molecular sciences$$v25$$x1422-0067$$y2024
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