ZER1

Last update 08 May 2025

Basic Info

Synonyms

C9orf60, Hzyg, Protein zer-1 homolog

+ [6]

Introduction

Serves as substrate adapter subunit in the E3 ubiquitin ligase complex ZYG11B-CUL2-Elongin BC (PubMed:17304241, PubMed:31273098). Acts to target substrates bearing N-terminal degrons for proteasomal degradation with the first four residues of substrates being the key recognition elements (PubMed:33093214, PubMed:34214466, PubMed:36496439). Involved in the clearance of proteolytic fragments generated by caspase cleavage during apoptosis since N-terminal glycine degrons are strongly enriched at caspase cleavage sites. Also important in the quality control of protein N-myristoylation in which N-terminal glycine degrons are conditionally exposed after a failure of N-myristoylation (PubMed:31273098).

100 Clinical Results associated with ZER1

100 Translational Medicine associated with ZER1

0 Patents (Medical) associated with ZER1

Literatures (Medical) associated with ZER1

22 Aug 2024·Journal of Medicinal Chemistry

Distinct Amino Acid-Based PROTACs Target Oncogenic Kinases for Degradation in Non-Small Cell Lung Cancer (NSCLC)

Article

Author: Rao, Hai ; Chen, Congli ; Fang, Lijing ; Liu, Chaowei ; Zhang, Jianchao ; Song, Xiaoxiao ; Chen, Xiao ; Tan, Chris Soon Heng ; Li, Fengming ; Liao, Kefan ; Su, Ming-Yuan

Proteolysis-targeting chimeras (PROTACs) selectively eliminate detrimental proteins by exploiting the ubiquitin-proteasome system (UPS), representing a promising therapeutic strategy against various diseases. Effective adaptations of degradation signal sequences and E3 ligases for PROTACs remain limited. Here, we employed three amino acids─Gly, Pro, and Lys─as the ligand to recruit the corresponding E3 ligases: CRL2^ZYG11B/ZER1, GID4, and UBRs, to degrade EML4-ALK and mutant EGFR, two oncogenic drivers in NSCLC. We found that the extent of EML4-ALK and EGFR reduction can be easily fine-tuned by using different degradation signals. These amino acid-based PROTACs, termed AATacs, hindered proliferation and induced cell cycle arrest and apoptosis of NSCLC cells in vitro. Compared to other PROTACs, AATacs are small, interchangeable but with different degradation efficiency. Our study further expands the repertoire of E3 ligases and their ligands for PROTAC application, improving the versatility and utility of targeted protein degradation for therapeutic purposes.

30 Jun 2023·Journal of thoracic disease

Target genes of N6-methyladenosine regulatory protein ALKBH5 are associated with prognosis of patients with lung adenocarcinoma.

Article

Author: Qiu, Yuan ; Lu, Weixiang ; Huang, Ying ; Wang, Wenjun ; Lan, Lan ; Jiang, Long

BackgroundLung adenocarcinoma (LUAD) exhibits high fatality rates, and effective treatments are lacking. The expression of the N6-methyladenosine (m6A) regulatory protein ALKBH5 is associated with lung cancer. To identify new therapeutic targets for LUAD, we screened target genes of ALKBH5 and analyzed their potential mechanisms of action.MethodsLUAD samples from The Cancer Genome Atlas (TCGA) were used to analyze the expression of ALKBH5 and screen for genes with correlated expression. Intersection of the genes upregulated in cells with ALKBH5 silencing with the genes significantly associated with ALKBH5 were defined as ALKBH5 target genes. STRING was used to evaluate interactions between the target genes, and the relationship between ALKBH5 target gene expression and LUAD patient prognosis was analyzed using the R package Survminer. Target genes were evaluated by functional enrichment analyses.ResultsALKBH5 was highly expressed in LUAD tissues and was significantly associated with a poor prognosis. Fifteen ALKBH5 target genes were identified, primarily enriched in protein processing in the endoplasmic reticulum, transcriptional coregulator activity, and cell activation involved in the immune response. Upregulation of ZNF777, TCOF1, CPLX2, and ABL1 was associated with a poor prognosis, whereas upregulation of ZER1, VPS53, and RRBP1 was associated with a good prognosis.ConclusionsThis study provides potential therapeutic targets for LUAD and a basis for further studies on the mechanism underlying the effects of ALKBH5.

01 Aug 2021·Molecular CellQ1 · BIOLOGY

Molecular basis for recognition of Gly/N-degrons by CRL2ZYG11B and CRL2ZER1

Q1 · BIOLOGY

Article

Author: Mi, Wenyi ; Yan, Xiaojie ; Li, Yao ; Zhao, Yueling ; Dong, Cheng ; Ma, Zhenyi ; Zhou, Zhili ; Song, Guangyong ; Wang, Guobin ; Feng, Qiqi

N-degron pathways are a set of proteolytic systems that target the N-terminal destabilizing residues of substrates for proteasomal degradation. Recently, the Gly/N-degron pathway has been identified as a new branch of the N-degron pathway. The N-terminal glycine degron (Gly/N-degron) is recognized by ZYG11B and ZER1, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2). Here we present the crystal structures of ZYG11B and ZER1 bound to various Gly/N-degrons. The structures reveal that ZYG11B and ZER1 utilize their armadillo (ARM) repeats forming a deep and narrow cavity to engage mainly the first four residues of Gly/N-degrons. The α-amino group of the Gly/N-degron is accommodated in an acidic pocket by five conserved hydrogen bonds. These structures, together with biochemical studies, decipher the molecular basis for the specific recognition of the Gly/N-degron by ZYG11B and ZER1, providing key information for future structure-based chemical probe design.

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ZER1

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