AMOT

Last update 08 May 2025

Basic Info

Synonyms

AMOT, angiomotin, KIAA1071

Introduction

Plays a central role in tight junction maintenance via the complex formed with ARHGAP17, which acts by regulating the uptake of polarity proteins at tight junctions. Appears to regulate endothelial cell migration and tube formation. May also play a role in the assembly of endothelial cell-cell junctions. Repressor of YAP1 and WWTR1/TAZ transcription of target genes, potentially via regulation of Hippo signaling-mediated phosphorylation of YAP1 which results in its recruitment to tight junctions (PubMed:21205866).

100 Clinical Results associated with AMOT

100 Translational Medicine associated with AMOT

0 Patents (Medical) associated with AMOT

214

Literatures (Medical) associated with AMOT

26 Mar 2025·Science Translational Medicine

TRIM15 drives chondrocyte senescence and osteoarthritis progression

Article

Author: Ji, Ming-liang ; Hu, Xinyue ; Li, Zhuang ; Zhang, Weituo ; Lu, Jun ; Wei, Xiao ying ; Shen, Shuying ; Hu, Jun zheng ; Liu, Haoyang

Osteoarthritis (OA) is a prevalent joint disease characterized by pain, disability, and loss of physical function, posing a challenge to public health. However, molecular mechanisms of OA pathogenesis have not been fully described. We report that tripartite motif containing 15 (TRIM15) is a regulator in chondrocyte senescence and OA. Our study revealed heightened expression of TRIM15 in chondrocytes of senescent cartilage from patients with OA and in aged wild-type mice. Using gain- and loss-of-function studies, we found that TRIM15 facilitated human chondrocyte senescence. Conditional deletion of Trim15 in mouse chondrocytes severely impaired skeletal growth, partially because of impaired embryonic chondrocyte senescence. Compared with conditionally knocked out Col2a1-CreER T2 /Trim15 flox/flox mice, Trim15flox/flox control mice exhibited accelerated OA phenotypes, increased senescence markers, and senescence-associated secretory phenotype during aging. Mechanistically, TRIM15 bound with yes-associated protein (YAP) and mediated K48-linked YAP ubiquitination at K254, which interrupted the interaction between YAP and angiomotin, leading to enhanced YAP nuclear translocation. Dysregulation of TRIM15-YAP and transcriptional coactivator with PDZ-binding motif (TAZ) signaling promoted OA progression in both the surgery-induced and natural aging–induced mouse OA model. Intra-articular injection of adeno-associated virus 5 (AAV5)– Trim15 shRNA decelerated OA progression in mice. In particular, YAP and TAZ protein amounts were increased in chondrocytes of patients with OA. Our preclinical results demonstrated that the AAV5- TRIM15 shRNA treatment protected human OA explants against degeneration through inhibiting chondrocyte senescence. Together, our findings underscore the potential of targeting TRIM15 in reshaping the aging cartilage microenvironment and suggest a promising therapeutic avenue for OA.

01 Mar 2025·Archives of Biochemistry and Biophysics

Live-cell FRET assay on the stoichiometry and affinity of the YAP complexes in MCF-7 cells

Article

Author: Fan, Xuhong ; Chen, Tongsheng ; Li, Xin ; Wu, Guihao ; Ni, Yue ; Fu, Ze ; Dai, Lingao ; Wu, Ge ; Wang, Xiaoping ; Zhan, Yongtong

Yes-associated protein (YAP), a focal point of current biological research, is involved in regulating various life processes. In this report, live-cell fluorescence resonance energy transfer (FRET) imaging was employed to unravel the YAP complexes in MCF-7 cells. Fluorescence imaging of living cells co-expressing CFP (cyan fluorescent protein)-YAP and YFP (yellow fluorescent protein)-LATS1 (large tumor suppressor 1) plasmids revealed that YAP promoted LATS1 oligomerization around mitochondria. Moreover, FRET two-hybrid assay showed that YAP directly interacted with LATS1 to form dimer. Similarly, we found that YAP directly interacted with large tumor suppressor 2 (LATS2) to form a heterotrimer with 1:2 in cytoplasm and around mitochondria. In addition, YAP directly interacted with angiomotin (AMOT) to form a heterodimer in cytoplasm. However, YAP did not interact with O-linked N-acetylglucosamine transferase (OGT). Furthermore, FRET assay also indicated that YAP exhibited a higher affinity with AMOT, followed by LATS1, and least with LATS2. In summary, YAP directly interacts with LATS1 and AMOT to form a heterodimer, with LATS2 to form a heterotrimer with 1:2, and shows a preference for binding to AMOT, followed by LATS1, and lastly LATS2, providing new insights into the Hippo-YAP signaling pathway.

01 Jan 2025·Developmental Biology

Blastocoel expansion and AMOT degradation cooperatively promote YAP nuclear localization during epiblast formation

Article

Author: Sasaki, Hiroshi ; Maeda, Hinako ; Hinako, Maeda

The epiblast is a pluripotent cell population formed in the late blastocyst stage of preimplantation embryos. During the process of epiblast formation from the inner cell mass (ICM) of the early blastocyst, activation of the Hippo pathway transcription factor TEAD by the nuclear translocation of the coactivator protein YAP is required for the robust expression of pluripotency factors. However, the mechanisms that alter YAP localization during epiblast formation remain unknown. Here, we reveal two such mechanisms. Expansion of the blastocoel promotes nuclear YAP localization by increasing cytoplasmic F-actin and reducing YAP phosphorylation. Additionally, cell differentiation regulates YAP. Expression of the junctional Hippo component, AMOT, gradually decreases during epiblast formation through a tankyrase-mediated degradation. SOX2 expression in the ICM is necessary for the reduction of AMOT and YAP phosphorylation. These two mechanisms function in parallel. Thus, the blastocoel-F-actin and SOX2-AMOT axes cooperatively suppress YAP phosphorylation and promote YAP nuclear localization during epiblast formation. The cooperation of these two distinct mechanisms likely contributes to the robustness of epiblast cell differentiation.

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