Ask about this productRelated genes to: AMOTL1 Blocking Peptide
- Gene:
- AMOTL1 NIH gene
- Name:
- angiomotin like 1
- Previous symbol:
- -
- Synonyms:
- JEAP
- Chromosome:
- 11q21
- Locus Type:
- gene with protein product
- Date approved:
- 2002-01-24
- Date modifiied:
- 2015-10-15
Related products to: AMOTL1 Blocking Peptide
Related articles to: AMOTL1 Blocking Peptide
- Angiomotin-like 1 (AMOTL1), by regulating cell-cell junctions, cell polarity, and cell migration, plays a critical role in organogenesis and development. Recently, multiple studies have identified two hotspot mutations in AMOTL1, Arg157 (R157) and Pro160 (P160), in more than ten distinct families presenting with a spectrum of congenital defects, including facial dysmorphisms and cardiac abnormalities. However, the underlying pathogenic mechanism remains elusive. R157 and P160 are located in the highly conserved Tankyrase-binding domain (TBD) of AMOTL1. Here, we show that both the R157C and P160L mutants fail to interact with Tankyrase 1/2 (TNKS1/2) and Ring finger protein 146 (RNF146), rendering them unable to undergo PARylation (poly ADP-ribosylation), ubiquitination, and subsequent proteasomal degradation. As a result, these mutants are significantly stabilized and accumulate in the cytoplasm. Accumulated AMOTL1 mutants, in turn, disrupt cell junctions and focal adhesions, thereby inhibiting both the velocity and persistence of cell migration. Furthermore, during zebrafish embryonic development, expression of the R157C mutant leads to craniofacial malformations and defects in cardiac function and skeletal muscle. Our study confirms the role of AMOTL1mutations in tissue development and uncovers the pathogenic mechanism at both molecular and cellular levels. - Source: PubMed
Publication date: 2026/04/21
Luo JiaqianJin RuxinGeng FangWang YunyingZhu YuwenGao WenqiangGao WeiLi JianJiu YamingZhang RuilinYu Fa-XingWang Yu - Aerobic glycolysis drives cancer progression through phosphofructokinase (PFK)-mediated regulation. The contribution of platelet-type PFK (PFKP) to head and neck squamous cell carcinoma (HNSCC) pathogenesis remains undefined. - Source: PubMed
Publication date: 2026/02/13
Wang LingwaLi HaiyangYang YifanShi QianFeng LingWang RuFang Jugao - The Hippo signaling pathway regulates the homeostatic balance between cell growth and apoptosis through intricate networks of multivalent protein complexes. How multivalency modulates the assembly and stability of these protein complexes remains poorly understood. Here, we show that Angiomotin-like 1 (AMOTL1), a scaffold protein containing three PPxY motifs, employs distinct cooperative binding mechanisms to engage two WW domain-containing partners: NEDD4-1, which promotes AMOTL1 degradation, and KIBRA, which protects AMOTL1 from degradation. Using quantitative molecular biophysical analyses, including isothermal titration calorimetry and nuclear magnetic resonance spectroscopy, we demonstrate that AMOTL1 forms a cooperatively stabilized complex with NEDD4-1 through simultaneous engagement of all three PPxY motifs with three of the four NEDD4-1 WW domains. This cooperative binding mode produces approximately ten-fold enhancement in affinity compared to the primary anchor interaction alone. In contrast, KIBRA engages AMOTL1 primarily through high-affinity binding at the C-terminal PPxY motif, with transient secondary interactions at the other PPxY sites that do not enhance overall binding strength. These contrasting mechanisms demonstrate that multivalency within the Hippo pathway serves as a tunable regulatory feature, where cooperative interactions can either enhance or minimally contribute to binding strength, explaining how a single scaffold protein can be differentially regulated to achieve opposing functional outcomes. - Source: PubMed
Publication date: 2026/01/22
Vogel AmberMcWhorter MatthewKwok EthieneNyarko Afua - The bacterial pathogen delivers more than 330 effector proteins into host cells through its Dot/Icm type IV secretion system (T4SS) to facilitate its intracellular replication. A number of these effectors modulate organelle trafficking pathways to create a membrane-bound niche called the -containing vacuole (LCV). In this study, we found that induces F-actin accumulation in the host cell cortex by its Dot/Icm substrate RavJ (Lpg0944). RavJ harbors a CHD motif associated with human tissue transglutaminases (TGs). We show that RavJ catalyzes a covalent linkage between actin and members of the Motin family of proteins, including Angiomotin (AMOT) and Angiomotin-like 1 (AMOTL1), which are known to regulate cell migration and contribute to the formation of cellular structures such as endothelial cell junctions and tubes. Further study reveals that RavJ-induced crosslink between actin and AMOT occurs on its Gln residue. Crosslink between actin and AMOT significantly reduces the binding between actin and its binding partner cofilin, suggesting that RavJ inhibits actin depolymerization. We also demonstrate that the metaeffector LegL1 directly interacts with RavJ to antagonize its TG activity, leading to reduced crosslinks between actin and Motin proteins. Our results reveal a novel mechanism of modulating the host actin cytoskeleton by . - Source: PubMed
Publication date: 2025/06/18
Liu YanLiu YaoLuo Zhao-Qing - Placental DNA methylation varies across gestation and is associated with obstetrical complications. Cell-free DNA (cfDNA) from maternal plasma could provide a noninvasive approach to study placental DNA methylation in ongoing pregnancies. However, research on maternal cfDNA methylation is limited and technologically challenging. Therefore, we aimed to investigate DNA methylation in maternal cfDNA and placental tissues across gestation using the innovative methylation DNA sequencing (MeD-seq) technology. Secondly, we explored the origins of methylation differences in maternal cfDNA across gestation, and aimed to identify gestational age-associated placental DNA methylation markers directly in cfDNA. We longitudinally collected maternal cfDNA in all three trimesters and at birth (n = 10), alongside placental tissues from first trimester, second trimester, and term pregnancies (all n = 10), and used previously collected maternal blood buffy coat samples (n = 20). Different placental cell types, including syncytiotrophoblasts/cytotrophoblasts (SCTs/CTBs) (n = 10), extravillous trophoblasts (n = 7), and syncytial knotting (n = 3), and maternal cell types including spiral arteries (n = 3) and endometrial epithelium (n = 3), were isolated using laser capture microdissection. Differentially methylated regions (DMRs) identified in cfDNA from pregnant compared to non-pregnant women (n = 6) ranged from 798 to 2163 in first and third trimesters, respectively. Gradual DNA methylation changes were observed across gestation in cfDNA, placental tissues, and trophoblasts. We showed an increase in DMRs in cfDNA, that overlap with DNA methylation in placental tissues and especially trophoblasts, and in DNA methylation of placenta-specific markers across gestation, reflecting an increased placental-originated cfDNA fraction. Among 110 DMRs between first trimester and term placental tissues, those related to NXPH4, EPS8L2, AMOTL1, and IRX2 had the strongest association with gestational age in cfDNA, for which comparable associations were found in SCTs/CTBs. These DMRs were all hypomethylated in maternal buffy coat samples. This study indicates the feasibility of identifying gestational age-dependent placental DNA methylation marks in maternal cfDNA and can serve as a reference for future studies. - Source: PubMed
van Vliet Marjolein MBoers Ruben GBoers Joachim BSchäffers Olivier J Mvan der Meeren Lotte EGribnau JoostSchoenmakers SamSteegers-Theunissen Régine P M