ZO Proteins Redundantly Regulate the Transcription Factor DbpA/ZONAB

Abstract

Background: ZO-1 overexpression inhibits DbpA/ZONAB overactivation, suggesting that ZO-1 sequesters DbpA at junctions. Results: Simultaneous depletion of ZO-1, ZO-2, and ZO-3 is required to decrease DbpA localization at junctions. Conclusion:The junctional localization of DbpA is regulated redundantly by ZO proteins. Significance: Clarifying how junctional transcription factors are regulated is essential to understand epithelial proliferation.

ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture

“…Further, interluminal septae in ZO-1 KD cysts persisted, indicating that the multi-lumen phenotype is not merely a consequence of an inadequately expanded single lumen. Consistent with this, ZO-1/ZO-2 double-KD cells, which have a more severe paracellular barrier phenotype than ZO-1 single KD cells (Rodgers et al, 2013;Spadaro et al, 2014;Van Itallie et al, 2009), formed single-lumen cysts ( Fig Multiple ZO-1 domains contribute to the genesis of singlelumen cysts…”

Bradykinin increased the permeability of BTB via NOS/NO/ZONAB-mediating down-regulation of claudin-5 and occludin

“…ZONAB is an epithelial-specific transcription factor and the localization and activities of it are partially regulated by the density-dependent assembly of epithelial junctions [20]. The research on the function of ZONAB is mainly focused on ZONAB regulating cellular proliferation and differentiation.…”

Cell–Cell Junctions Organize Structural and Signaling Networks

“…Once the cells terminally differentiate, they migrate continuously to the top of the villus where they undergo apoptosis and are extruded from the epithelium into the intestinal lumen. Cell-cell junctions play indirect roles in regulating cell proliferation by sequestering specific transcription factors at the plasma membrane: ZO-1 and ZONAB (Balda et al 2003), cadherins and beta-catenin (Nelson and Nusse 2004), and ZO-2 and YAP1 (Oka et al 2010; Spadaro et al 2014). Figure 2B provides examples of the roles of each of these interactions, in addition to specific details below.…”

“…ZONAB target genes include proliferative cell nuclear antigen (PCNA) and cyclin D1, which control cell proliferation (Balda et al 2003; Sourisseau et al 2006; Tsapara et al 2006; Gonzalez-Mariscal et al 2014). Depletion of ZO-1 and ZO-2 results in loss of ZONAB from the TJ and its degradation (Spadaro et al 2014). The PDZ1 domain of ZO-2 also binds to another transcription factor, Yes-associated-protein (YAP), and facilitates YAP shuttling from the cytoplasm into the nucleus (Oka et al 2010; Spadaro et al 2014).…”

“…Depletion of ZO-1 and ZO-2 results in loss of ZONAB from the TJ and its degradation (Spadaro et al 2014). The PDZ1 domain of ZO-2 also binds to another transcription factor, Yes-associated-protein (YAP), and facilitates YAP shuttling from the cytoplasm into the nucleus (Oka et al 2010; Spadaro et al 2014). The ZO-2-YAP interaction may induce a pro-apoptotic or pro-cell growth response depending on the physiological context (Oka et al 2010; Dominguez-Calderon et al 2016).…”