Myc-interacting zinc-finger protein 1 positively regulates Wnt signalling by protecting Dishevelled from Dapper1-mediated degradation

Wnt signalling regulates embryonic development and tissue homoeostasis by modulating cell proliferation, differentiation and migration. Dapper1 (Dpr1) has been shown to be an important key negative regulator of Wnt signalling by promoting Dishevelled (Dvl) degradation. In the present study, we found that Myc-interacting zinc-finger protein 1 (MIZ1) interacts with Dpr1 and this interaction attenuates the ability of Dpr1 to induce Dvl2 degradation, thus enhancing Wnt signalling. Mechanistically, MIZ1 is translocated from the nucleus to the cytoplasm upon Wnt3a stimulation or overexpression of Dpr1 and Dvl2, disrupting the interaction between Dpr1 and Dvl2. Furthermore, MIZ1 can promote the proliferation of breast cancer MDA-MB-231 and BT-549 cells through Wnt signalling and reverse the anti-proliferative effect of Dpr1 on colorectal cancer Caco-2. Together, our findings establish a novel layer of Wnt signalling regulation via the MIZ1–Dpr1–Dvl axis.

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Inhibition of zinc finger protein 367 exerts a tumor suppressive role in colorectal cancer by affecting the activation of oncogenic YAP1 signaling

Environmental Toxicology ◽

10.1002/tox.23341 ◽

2021 ◽

Author(s):

Ting Lei ◽

Ya Gao ◽

Yuhong Duan ◽

Chunli Cui ◽

Li Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Zinc Finger ◽

Zinc Finger Protein ◽

Finger Protein

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Zinc-finger protein MdBBX7/MdCOL9, a target of MdMIEL1 E3 ligase, confers drought tolerance in apple

Plant Physiology ◽

10.1093/plphys/kiab420 ◽

2021 ◽

Author(s):

Pengxiang Chen ◽

Fang Zhi ◽

Xuewei Li ◽

Wenyun Shen ◽

Mingjia Yan ◽

...

Keyword(s):

Drought Stress ◽

Drought Tolerance ◽

Zinc Finger ◽

Zinc Finger Protein ◽

E3 Ligase ◽

26S Proteasome ◽

Negative Regulator ◽

Binding Motif ◽

Ethylene Response Factor ◽

Finger Protein

Abstract Water deficit is one of the main challenges for apple (Malus × domestica) growth and productivity. Breeding drought-tolerant cultivars depends on a thorough understanding of the drought responses of apple trees. Here, we identified the zinc-finger protein B-BOX 7/CONSTANS-LIKE 9 (MdBBX7/MdCOL9), which plays a positive role in apple drought tolerance. The overexpression of MdBBX7 enhanced drought tolerance, whereas knocking down MdBBX7 expression reduced it. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis identified one cis-element of MdBBX7, CCTTG, as well as its known binding motif, the T/G box. ChIP-seq and RNA-seq identified 1,197 direct targets of MdBBX7, including ETHYLENE RESPONSE FACTOR (ERF1), EARLY RESPONSIVE TO DEHYDRATION 15 (ERD15), and GOLDEN2-LIKE 1 (GLK1) and these were further verified by ChIP-qPCR and electronic mobility shift assays. Yeast two-hybrid screen identified an interacting protein of MdBBX7, RING-type E3 ligase MYB30-INTERACTING E3 LIGASE 1 (MIEL1). Further examination revealed that MdMIEL1 could mediate the ubiquitination and degradation of MdBBX7 by the 26S proteasome pathway. Genetic interaction analysis suggested that MdMIEL1 acts as an upstream factor of MdBBX7. In addition, MdMIEL1 was a negative regulator of the apple drought stress response. Taken together, our results illustrate the molecular mechanisms by which the MdMIEL1–MdBBX7 module influences the response of apple to drought stress.

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