Angiomotin (AMOT) and Angiomotin-like protein 2 (AMOTL2) (AMOT/AMOTL2)

Angiomotin (AMOT) and Angiomotin-like protein 2 (AMOTL2) are essential scaffolding proteins within the Motin family that play a central role in the Hippo signaling pathway, cell polarity, and angiogenesis [4, 5]. They function by interacting with the transcriptional co-activators YAP and TAZ, either sequestering them in the cytoplasm to inhibit growth or, in certain contexts, promoting their nuclear translocation to drive proliferation [9, 15]. These proteins are also critical for maintaining tight junctions and organizing the actin cytoskeleton, which are vital for endothelial cell migration and vascular tube formation [2, 12]. In oncology, AMOT and AMOTL2 exhibit complex, context-dependent roles; they act as oncogenes in breast and liver cancers but function as tumor suppressors in glioblastoma and lung cancer [4, 12]. Therapeutic interest focuses on targeting these proteins to inhibit pathological angiogenesis or to modulate YAP/TAZ activity in YAP-driven malignancies [2, 19]. Experimental approaches include the use of monoclonal antibodies, tankyrase inhibitors to stabilize the proteins, and BET inhibitors to target specific invasive isoforms like p60AmotL2 [2, 13, 19]. Additionally, AMOTL2 has been implicated in cardiovascular conditions such as pulmonary arterial hypertension, where its upregulation can ameliorate disease progression by inactivating YAP1 signaling [14].

Other names

AngiomotinAngiomotin-like protein 2AMOTAMOTL2LCCPMASCOTMotin family proteins

Modulation of YAP/TAZ nuclear translocation and transcriptional activity; inhibition of endothelial cell migration and tube formation; stabilization of tight junctions; regulation of alternative splicing.