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Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling

(2010) BIOCHEMICAL JOURNAL. 432(3). p.461-472
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Abstract
he Hippo pathway regulates the size of organs by controlling two opposing processes: proliferation and apoptosis. YAP2 (Yes kinase-associated protein 2), one of the three isoforms of YAP, is a WW domain-containing transcriptional co-activator that acts as the effector of the Hippo pathway in mammalian cells. In addition to WW domains, YAP2 has a PDZ-binding motif at its C-terminus. We reported previously that this motif was necessary for YAP2 localization in the nucleus and for promoting cell detachment and apoptosis. In the present study, we show that the tight junction protein ZO (zonula occludens)-2 uses its first PDZ domain to form a complex with YAP2. The endogenous ZO-2 and YAP2 proteins co-localize in the nucleus. We also found that ZO-2 facilitates the nuclear localization and pro-apoptotic function of YAP2, and that this activity of ZO-2 is PDZ-domain-dependent. The present paper is the first report on a PDZ-based nuclear translocation mechanism. Moreover, since the Hippo pathway acts as a tumour suppressor pathway, the YAP2-ZO-2 complex could represent a target for cancer therapy.
Keywords
PDZ domain, nuclear translocation, Hippo pathway, OCCLUDIN, BINDING, TUMOR-SUPPRESSOR, ZONULA OCCLUDENS-1, TRANSCRIPTIONAL ACTIVATOR, EPITHELIAL-CELLS, HIPPO PATHWAY, WW DOMAIN, TIGHT JUNCTION, YES-ASSOCIATED PROTEIN, Yes kinase-associated protein 2 (YAP2), zona occludens protein

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Chicago
Oka, Tsutomu, Eline Remue, Kris Meerschaert, Berlinda Vanloo, Ciska Boucherie, David Gfeller, Gary D Bader, et al. 2010. “Functional Complexes Between YAP2 and ZO-2 Are PDZ Domain-dependent, and Regulate YAP2 Nuclear Localization and Signalling.” Biochemical Journal 432 (3): 461–472.
APA
Oka, T., Remue, E., Meerschaert, K., Vanloo, B., Boucherie, C., Gfeller, D., Bader, G. D., et al. (2010). Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling. BIOCHEMICAL JOURNAL, 432(3), 461–472.
Vancouver
1.
Oka T, Remue E, Meerschaert K, Vanloo B, Boucherie C, Gfeller D, et al. Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling. BIOCHEMICAL JOURNAL. 2010;432(3):461–72.
MLA
Oka, Tsutomu, Eline Remue, Kris Meerschaert, et al. “Functional Complexes Between YAP2 and ZO-2 Are PDZ Domain-dependent, and Regulate YAP2 Nuclear Localization and Signalling.” BIOCHEMICAL JOURNAL 432.3 (2010): 461–472. Print.
@article{1256657,
  abstract     = {he Hippo pathway regulates the size of organs by controlling two opposing processes: proliferation and apoptosis. YAP2 (Yes kinase-associated protein 2), one of the three isoforms of YAP, is a WW domain-containing transcriptional co-activator that acts as the effector of the Hippo pathway in mammalian cells. In addition to WW domains, YAP2 has a PDZ-binding motif at its C-terminus. We reported previously that this motif was necessary for YAP2 localization in the nucleus and for promoting cell detachment and apoptosis. In the present study, we show that the tight junction protein ZO (zonula occludens)-2 uses its first PDZ domain to form a complex with YAP2. The endogenous ZO-2 and YAP2 proteins co-localize in the nucleus. We also found that ZO-2 facilitates the nuclear localization and pro-apoptotic function of YAP2, and that this activity of ZO-2 is PDZ-domain-dependent. The present paper is the first report on a PDZ-based nuclear translocation mechanism. Moreover, since the Hippo pathway acts as a tumour suppressor pathway, the YAP2-ZO-2 complex could represent a target for cancer therapy.},
  author       = {Oka, Tsutomu and Remue, Eline and Meerschaert, Kris and Vanloo, Berlinda and Boucherie, Ciska and Gfeller, David and Bader, Gary D and Sidhu, Sachdev S and Vandekerckhove, Jo{\"e}l and Gettemans, Jan and Sudol, Marius},
  issn         = {0264-6021},
  journal      = {BIOCHEMICAL JOURNAL},
  keyword      = {PDZ domain,nuclear translocation,Hippo pathway,OCCLUDIN,BINDING,TUMOR-SUPPRESSOR,ZONULA OCCLUDENS-1,TRANSCRIPTIONAL ACTIVATOR,EPITHELIAL-CELLS,HIPPO PATHWAY,WW DOMAIN,TIGHT JUNCTION,YES-ASSOCIATED PROTEIN,Yes kinase-associated protein 2 (YAP2),zona occludens protein},
  language     = {eng},
  number       = {3},
  pages        = {461--472},
  title        = {Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling},
  url          = {http://dx.doi.org/10.1042/BJ20100870},
  volume       = {432},
  year         = {2010},
}

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