Unknown

Dataset Information

0

Atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 controls the core epithelial-to-mesenchymal transition-inducing transcription factors.


ABSTRACT: Epithelial-mesenchymal transition (EMT) plays a critical role in the development of tumor metastases by enhancing migration/invasion. One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by the core EMT-inducing transcription factors (EMT-TFs), such as Zeb1/2, Snai1/2 and Twist1. Here, we find that EMT-TFs can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbxo45) through the ubiquitin proteasome system (UPS). The key step is recognition of EMT-TFs by Fbxo45 through its SPRY domain for Zeb2, or F-box domain for the other three EMT-TFs Snai1, Snai2 and Twist1, respectively. The K48-linkaged ubiquitination capability on Zeb2 relies on its functional SBD domain. In addition, miR-27a* can directly down-regulate the expression of Fbxo45, preventing degradation of EMT-TFs and thus ensuring EMT phenotype. We suggest that Fbxo45 is a key node of the miR-27a*/Fbxo45/EMT-TFs signaling axis.

SUBMITTER: Xu M 

PROVIDER: S-EPMC4359269 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 controls the core epithelial-to-mesenchymal transition-inducing transcription factors.

Xu Ming M   Zhu Changhong C   Zhao Xian X   Chen Cheng C   Zhang Hailong H   Yuan Haihua H   Deng Rong R   Dou Jinzhuo J   Wang Yanli Y   Huang Jian J   Chen Qin Q   Jiang Bin B   Yu Jianxiu J  

Oncotarget 20150101 2


Epithelial-mesenchymal transition (EMT) plays a critical role in the development of tumor metastases by enhancing migration/invasion. One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by the core EMT-inducing transcription factors (EMT-TFs), such as Zeb1/2, Snai1/2 and Twist1. Here, we find that EMT-TFs can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbxo45) through the ubiquitin proteasome system (  ...[more]

Similar Datasets

| S-EPMC6791387 | biostudies-literature
| S-EPMC5682971 | biostudies-literature
| S-EPMC6130950 | biostudies-literature
| S-EPMC2823526 | biostudies-other
| S-EPMC9320552 | biostudies-literature
| S-EPMC2435383 | biostudies-literature
| S-EPMC10781586 | biostudies-literature
| S-EPMC2708094 | biostudies-literature
| S-EPMC2757842 | biostudies-other
2015-07-10 | E-GEOD-70658 | biostudies-arrayexpress