Regulation of TP73 transcription by Hippo-YAP signaling

Wen, Zichao; Wang, Yu; Qi, Sixian; Ma, Mingyue; Li, Jian; Yu, Fa‐Xing

doi:10.1016/j.bbrc.2020.07.132

Cited by 3 publications

(2 citation statements)

References 41 publications

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“…Possible clues to the molecular mechanism include the following: LATS2 inactivation increases p73 transcription by TEAD, and knockdown of SMG6 further increases p73 expression through ATM stabilization (Fig. S5A ) [ 57 , 58 ]. These synergistic effects induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

SMG6 regulates DNA damage and cell survival in Hippo pathway kinase LATS2-inactivated malignant mesothelioma

et al. 2022

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Many genes responsible for Malignant mesothelioma (MM) have been identified as tumor suppressor genes and it is difficult to target these genes directly at a molecular level. We searched for the gene which showed synthetic lethal phenotype with LATS2, one of the MM causative genes and one of the kinases in the Hippo pathway. Here we showed that knockdown of SMG6 results in synthetic lethality in LATS2-inactivated cells. We found that this synthetic lethality required the nuclear translocation of YAP1 and TAZ. Both are downstream factors of the Hippo pathway. We also demonstrated that this synthetic lethality did not require SMG6 in nonsense-mediated mRNA decay (NMD) but in regulating telomerase reverse transcriptase (TERT) activity. In addition, the RNA-dependent DNA polymerase (RdDP) activity of TERT was required for this synthetic lethal phenotype. We confirmed the inhibitory effects of LATS2 and SMG6 on cell proliferation in vivo. The result suggests an interaction between the Hippo and TERT signaling pathways. We also propose that SMG6 and TERT are novel molecular target candidates for LATS2-inactivated cancers such as MM.

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Section: Discussionmentioning

confidence: 99%

SMG6 regulates DNA damage and cell survival in Hippo pathway kinase LATS2-inactivated malignant mesothelioma

et al. 2022

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“…15,22 Here, 22 human esophageal cancer-related proteins that have been reported as the upstream interacting partners of YAP were compiled in supporting information Table S1; they are functionally diverse, including signal transduction proteins (PRRG4 and PTCH1), protein kinases (LATS1/2 and ErbB4), transcription factors/ modulators (TP73, SMAD1 and RUNX1/2/3), phosphatases (PTPN14), scaffolding proteins (DVL1/2/3), and others (WBP1/2, AMOT and AMOTL1/2). 21,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] The canonical forms of primary sequences of these YAP-partner proteins were retrieved from the UniProt database, 42 from which totally 106 decapeptide segments containing PRM motif [P/L]Px[Y/P] were identified, including 34 PPxY-containing segments, 48 PPxP-containing segments, 6 LPxYcontaining segments, and 18 LPxP-containing segments; they were considered as the potential recognition site candidates of YAP WW1/2 domains for subsequent analysis.…”

Section: Yap-interacting Proteins and Proline-rich Peptide Segmentsmentioning

confidence: 99%

Systematic profiling and identification of the peptide‐mediated interactions between human Yes‐associated protein and its partners in esophageal cancer

Chen

Wang

et al. 2021

J of Molecular Recognition

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Human Yes-associated protein (YAP) is involved in the Hippo signaling pathway and serves as a coactivator to modulate gene expression, which contains a transactivation domain (TD) responsible for binding to the downstream TEA domain family (TEAD) of transcription factors and two WW1/2 domains that recognize the proline-rich motifs (PRMs) present in a variety of upstream protein partners through peptidemediated interactions (PMIs). The downstream YAP TD-TEAD interactions are closely associated with gastric cancer, and a number of therapeutic agents have been developed to target the interactions. In contrast, the upstream YAP WW1/2-partner interactions are thought to be involved in esophageal cancer but still remain largely unexplored. Here, we attempted to elucidate the complicated PMIs between the YAP WW1/2 domains and various PRMs of YAP-interacting proteins. A total of 106 peptide segments carrying the class I WW-binding motif [P/L]Px[Y/P] were

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YAP in development and disease: Navigating the regulatory landscape from retina to brain

Zhao,

Sun,

et al. 2024

Biomedicine & Pharmacotherapy

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Regulation of TP73 transcription by Hippo-YAP signaling

Cited by 3 publications

References 41 publications

SMG6 regulates DNA damage and cell survival in Hippo pathway kinase LATS2-inactivated malignant mesothelioma

SMG6 regulates DNA damage and cell survival in Hippo pathway kinase LATS2-inactivated malignant mesothelioma

Systematic profiling and identification of the peptide‐mediated interactions between human Yes‐associated protein and its partners in esophageal cancer

YAP in development and disease: Navigating the regulatory landscape from retina to brain

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