Overexpression of tomato RING E3 ubiquitin ligase gene SlRING1 confers cadmium tolerance by attenuating cadmium accumulation and oxidative stress

Wnt signalling is dependent on dishevelled proteins (DVL1-3), which assemble an intracellular Wnt signalosome at the plasma membrane. The levels of DVL1-3 are regulated by multiple Cullin-RING E3 ligases that mediate their ubiquitination and degradation. The BTB-Kelch protein KLHL12 was the first E3 ubiquitin ligase to be identified for DVL1-3, but the molecular mechanisms determining its substrate interactions have remained unknown. Here, we mapped the interaction of DVL1-3 to a ‘PGXPP' motif that is conserved in other known partners and substrates of KLHL12, including PLEKHA4, PEF1, SEC31 and DRD4. To determine the binding mechanism, we solved a 2.4 Å crystal structure of the Kelch domain of KLHL12 in complex with a DVL1 peptide that bound with low micromolar affinity. The DVL1 substrate adopted a U-shaped turn conformation that enabled hydrophobic interactions with all six blades of the Kelch domain β-propeller. In cells, the mutation or deletion of this motif reduced the binding and ubiquitination of DVL1 and increased its stability confirming this sequence as a degron motif for KLHL12 recruitment. These results define the molecular mechanisms determining DVL regulation by KLHL12 and establish the KLHL12 Kelch domain as a new protein interaction module for a novel proline-rich motif.

Download Full-text

RING-Between-RING E3 Ubiquitin Ligase

Encyclopedia of Signaling Molecules ◽

10.1007/978-3-319-67199-4_103325 ◽

2018 ◽

pp. 4744-4744

Keyword(s):

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Ring E3

Download Full-text

PpHOS1, a RING E3 ubiquitin ligase, interacts with PpWRKY22 in the BABA-induced priming defense of peach fruit against Rhizopus stolonifer

Postharvest Biology and Technology ◽

10.1016/j.postharvbio.2019.111029 ◽

2020 ◽

Vol 159 ◽

pp. 111029 ◽

Cited By ~ 2

Author(s):

Chunhong Li ◽

Jing Wang ◽

Nana Ji ◽

Changyi Lei ◽

Daxiang Zhou ◽

...

Keyword(s):

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Rhizopus Stolonifer ◽

Peach Fruit ◽

Ring E3

Download Full-text

TFEB activates Nrf2 by repressing its E3 ubiquitin ligase DCAF11 and promoting phosphorylation of p62

Scientific Reports ◽

10.1038/s41598-019-50877-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Jee-Yun Park ◽

Sunhyo Kim ◽

Hee Young Sohn ◽

Young Ho Koh ◽

Chulman Jo

Keyword(s):

Oxidative Stress ◽

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Biological Response ◽

Related Factor ◽

Mrna Levels ◽

Nuclear Factor ◽

Glutathione S Transferase ◽

First Time ◽

Cellular Stressors

Abstract Transcriptional factor EB (TFEB) and nuclear factor E2-related factor 2 (Nrf2) play crucial roles in the biological response against cellular stressors; however, their relationship has not yet been investigated. Here, we constructed human neuroglioma cell lines stably expressing TFEB. The expression of Nrf2-response genes, including heme oxygenase (HO)-1, glutathione-s-transferase-mu1 (GSTM1), and p62, was induced in the cell line, independent of oxidative stress. Of note, the protein level of Nrf2 was significantly increased, and its ubiquitinated fraction was reduced in stable cells compared to that in the control cells. Among E3 ubiquitin ligases known to be involved in the ubiquitination of Nrf2, DDB1 and Cullin4 associated factor 11 (DCAF11) was down-regulated at both protein and mRNA levels in stable cells, indicating that the repression of DCAF11 by TFEB may be mainly involved in the stabilization of Nrf2. In addition, the level of phosphorylated p62 at S349 was highly increased in stable cells compared to that in control cells, which could allow it to interfere with the association of Keap1 and Nrf2, thus stabilizing Nrf2. We suggest for the first time that TFEB could activate Nrf2 by increasing its stability under conditions devoid of oxidative stress.

Download Full-text