Table 2.
Direct and indirect regulators of YAP1 and TAZ
| Category | Name | Effect on YAP1 and/or TAZ | Brief description |
|---|---|---|---|
| Cell adhesion molecule | Fat4 | Down | Protocadherin |
| DCHS1 | Down | Protocadherin | |
| CD44 | Up | Hyaluronan receptor | |
| Receptor | Gs-coupled receptor | Down | Mediated by PKA and Rho |
| G12/13-, Gq/11-, Gi/o-coupled receptor | Up | Mediated by Rho | |
| LIF receptor | Down | Mediated by Scribble | |
| Membrane-associated protein, cell junction protein | Merlin/NF2 | Down | Interacts with α-catenin and Par3 |
| FRMD6/Willin | Down | Putative homolog of Drosophila expanded | |
| KIBRA | Down | Interacts with Merlin, AMOT, PTPN14, and LATS kinases | |
| AMOT (AMOT-p80, AMOT-p130, AMOTL1, AMOTL2) | Down or up | Interacts with Patj, Merlin, and Rich | |
| AMOT-p130, AMOTL1, and AMOTL2 interact with YAP1 and TAZ | |||
| Ajuba (Ajuba, LIMD1, WTIP) | Down or up | All three interact with LATS kinases. LIMD1 reduces YAP1 phosphorylation in MDCK cells, while Ajuba inreases it in mesothelioma cells | |
| ZO-2 | Down (TAZ) or up (YAP1) | Interacts with YAP1 and TAZ and promotes nuclear localization | |
| PTPN14 | Down | Interacts with YAP1 | |
| α-Catenin | Down | Blocks dephosphorylation of YAP1 | |
| Actin cytoskeleton | High mechanical stress | Up | Rho and CDC42 activation |
| Low mechanical stress | Down | F-actin capping/severing proteins | |
| Cross-talk with other signaling pathway | Wnt pathway | Up | Phosphorylated β-catenin promotes TAZ degradation |
| Wnt signaling increases PP1A-dependennt dephosphorylation of TAZ | |||
| β-Catenin mutant stabilizes YAP1 | |||
| Sonic hedgehog pathway | Up | Sonic hedgehog increases nuclear YAP1 via IRS | |
| Others | LKB1 | Down | Mediated by Scribble, MARK, and LATS2 |
| ILK | Up | Inhibits Merlin via MYPT1-PP1 | |
| PP2A | Up | Dephosphorylates YAP1 | |
| TAO-1 | Down | Activates MST2 | |
| SIK | Up | Phosphorylates WW45 | |
| RASSF | Down | RASSF1A, RASSF2, and RASSF5 function as upstream regulators of the Hippo pathway. RASSF6 works as a tumor suppressor in parallel to the Hippo pathway. RASSF4 may have a similar mode of function | |
| NPHP4 | Up (TAZ) | Inhibits the interaction between LATS1 and TAZ | |
| NPHP9 | Up (TAZ) | Translocates TAZ into the nucleus | |
| ASPP1 | Up (YAP1) | Blocks the interaction between YAP1 and LATS1 | |
| ASPP2 | Up (TAZ) | Promotes the interaction between TAZ and PP1A | |
| HIPK2 | Up (YAP1) | Increases YAP1 independently of LATS kinases | |
| ANKHD1 | Up (YAP1) | Forms a complex with YAP1 and is necessary for YAP1 full activity | |
| PML | Up (YAP1) | Stabilizes YAP1 by sumoylation and enhances p73-dependent anscription | |
| WRN | Down (YAP1) | Suppresses YAP1 expression |