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A Tight Junction-Associated Merlin-Angiomotin Complex Mediates Merlin's Regulation of Mitogenic Signaling and Tumor Suppressive Functions
Open accessAbstract
Summary The Merlin/NF2 tumor suppressor restrains cell growth and tumorigenesis by controlling contact-dependent inhibition of proliferation. We have identified a tight-junction-associated protein complex comprising Merlin, Angiomotin, Patj, and Pals1. We demonstrate that Angiomotin functions downstream of Merlin and upstream of Rich1, a small GTPase Activating Protein, as a positive regulator of Rac1. Merlin, through competitive binding to Angiomotin, releases Rich1 from the Angiomotin-inhibitory complex, allowing Rich1 to inactivate Rac1, ultimately leading to attenuation of Rac1 and Ras-MAPK pathways. Patient-derived Merlin mutants show diminished binding capacities to Angiomotin and are unable to dissociate Rich1 from Angiomotin or inhibit MAPK signaling. Depletion of Angiomotin in Nf2−/− Schwann cells attenuates the Ras-MAPK signaling pathway, impedes cellular proliferation in vitro and tumorigenesis in vivo.
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Cites
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
Dalgliesh, G. L., Furge, K., Greenman, C., Chen, L., Bignell, G., Butler, A., Davies, H., Edkins, S., Hardy, C., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08672 · Cited by 1,173 · cited 2×
“In particular, a recent systematic analysis has indicated thatNF2 mutations define a subtype of non-VHL mutated clear cell renal carcinomas (ccRCCs) and targeted deletion of Nf2 in mouse renal epithelia leads to invasive carcinoma by 6–10 months of age (Dalgliesh et al., 2010; Morris and McClatchey, 2009).”
Zhang, N., Bai, H., David, K. K., Dong, J., Zheng, Y., Cai, J., Giovannini, M., Liu, P., Anders, R. A., & Pan, D. (2010) · Developmental Cell · doi:10.1016/j.devcel.2010.06.015 · Cited by 804
Cited by
The Hippo pathway: regulators and regulations.
Yu, F.-X., & Guan, K.-L. (2013) · Genes & Development · doi:10.1101/gad.210773.112 · Cited by 1,231
The Hippo Signaling Pathway in Development and Disease
Zheng, Y., & Pan, D. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.06.003 · Cited by 867
Aerobic glycolysis tunes YAP/TAZ transcriptional activity
Enzo, E., Santinon, G., Pocaterra, A., Aragona, M., Bresolin, S., Forcato, M., Grifoni, D., Pession, A., Zanconato, F., Guzzo, G., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490379 · Cited by 414
Zhang, W., Nandakumar, N., Shi, Y., Manzano, M., Smith, A., Graham, G., Gupta, S., Vietsch, E. E., Laughlin, S. Z., Wadhwa, M., et al. (2014) · Science Signaling · doi:10.1126/scisignal.2005049 · Cited by 360
Self-citationDeRan, M., Yang, J., Shen, C.-H., Peters, E. C., Fitamant, J., Chan, P., Hsieh, M., Zhu, S., Asara, J. M., Zheng, B., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.036 · Cited by 316
“AMOT, AMOTL1, and AMOTL2 are tight junction proteins that inhibit YAP through three mechanisms: (1) binding to and sequestering YAP out of nuclei (Yi et al., 2011; Zhao et al., 2011); (2) binding to and enhancing Lats1/Lats2 activation (Paramasivam et al., 2011); and (3) reducing the stability of…”
Metadata
- Authors
- Yi, C., Troutman, S., Fera, D., Stemmer-Rachamimov, A., Avila, J. L., Christian, N., Persson, N. L., Shimono, A., Speicher, D. W., Marmorstein, R., Holmgren, L., & Kissil, J. L.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 19
- Issue
- 4
- Pages
- 527-540
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2051627999
- Cited by
- 260
- References
- 2
- FWCI
- 15.55
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yi, C., Troutman, S., Fera, D., Stemmer-Rachamimov, A., Avila, J. L., Christian, N., Persson, N. L., Shimono, A., Speicher, D. W., Marmorstein, R., Holmgren, L., & Kissil, J. L. (2011). A Tight Junction-Associated Merlin-Angiomotin Complex Mediates Merlin's Regulation of Mitogenic Signaling and Tumor Suppressive Functions. Cancer Cell. https://doi.org/10.1016/j.ccr.2011.02.017
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
