Abstract
Angiomotin-like 2 (AMOTL2) is a member of Angiomotin family proteins, which are potent inhibitors for the Hippo pathway effector YAP. However, additional cellular functions of AMOTL2 besides YAP inhibition are largely unknown. Here, we reported that AMOTL2 associates with and negatively regulates AKT. Mechanistically, AMOTL2 binds to AKT pleckstrin homology domain and interrupts AKT's membrane localization. Liver-specific depletion of AMOTL2 enlarged mouse liver and activated both YAP and AKT. Downregulation of AMOTL2 is found in human liver cancers, correlating with the concomitant activation of YAP and AKT. Together, our results provide novel insights into a dual tumor suppressive function of AMOTL2 by targeting both YAP and AKT in liver size control and cancer prevention.
MeSH terms
-
Angiomotins
-
Animals
-
Carrier Proteins / antagonists & inhibitors
-
Carrier Proteins / metabolism*
-
Cell Cycle Proteins
-
Down-Regulation / physiology
-
Female
-
Gene Deletion
-
HEK293 Cells
-
Hep G2 Cells
-
Hepatomegaly / pathology
-
Hippo Signaling Pathway
-
Humans
-
Liver Neoplasms / metabolism*
-
Liver Neoplasms / pathology
-
Liver Neoplasms, Experimental / metabolism*
-
Liver Neoplasms, Experimental / pathology
-
Mice
-
Mice, Knockout
-
Mice, Nude
-
Nuclear Proteins / metabolism*
-
Protein Serine-Threonine Kinases / metabolism
-
Proto-Oncogene Proteins c-akt / metabolism*
-
Transcription Factors / metabolism*
Substances
-
AMOTL2 protein, human
-
Angiomotins
-
Carrier Proteins
-
Cell Cycle Proteins
-
Nuclear Proteins
-
Transcription Factors
-
YY1AP1 protein, human
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-akt