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Zinc finger myeloid Nervy DEAF-1 type (ZMYND) domain containing proteins exert molecular interactions to implicate in
Longji Wu1,2,3, Jing Huang1,2, Pankaj Trivedi4
1Department of Pathophysiology, School of Basic Medicine, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Songshan Lake Scientific and Industrial Park, Dongguan, 523808, Guangdong, People's Republic of China.
Abstract:
Morphogenesis and organogenesis in the low organisms have been found to be modulated by a number of proteins, and one of such factor, deformed epidermal auto-regulatory factor-1 (DEAF-1) has been initially identified in Drosophila. The mammalian homologue of DEAF-1 and structurally related proteins have been identified, and they formed a family with over 20 members. The factors regulate gene expression through association with co-repressors, recognition of genomic marker, to exert histone modification by catalyze addition of some chemical groups to certain amino acid residues on histone and non-histone proteins, and degradation host proteins, so as to regulate cell cycle progression and execution of cell death. The formation of fused genes during chromosomal translocation, exemplified with myeloid transforming gene on chromosome 8 (MTG8)/eight-to-twenty one translocation (ETO) /ZMYND2, MTG receptor 1 (MTGR1)/ZMYND3, MTG on chromosome 16/MTGR2/ZMYND4 and BS69/ZMYND11 contributes to malignant transformation. Other anomaly like copy number variation (CNV) of BS69/ZMYND11 and promoter hyper methylation of BLU/ZMYND10 has been noted in malignancies. It has been reported that when fusing with Runt-related transcription factor 1 (RUNX1), the binding of MTG8/ZMYND2 with co-repressors is disturbed, and silencing of BLU/ZMYND10 abrogates its ability to inhibition of cell cycle and promotion of apoptotic death. Further characterization of the implication of ZMYND proteins in carcinogenesis would enhance understanding of the mechanisms of occurrence and early diagnosis of tumors, and effective antitumor efficacy.
Insights
The ZMYND protein family, involved in gene regulation and cell cycle control, plays a role in cancer development. Understanding ZMYND proteins aids in tumor diagnosis and treatment.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Deformed epidermal auto-regulatory factor-1 (DEAF-1) and its homologs form a large family of proteins in mammals.
- These ZMYND proteins regulate gene expression via co-repressors, histone modification, and protein degradation.
- Dysregulation of ZMYND proteins is implicated in various cancers.
Purpose of the Study:
- To explore the role of ZMYND proteins in carcinogenesis.
- To understand the mechanisms underlying tumor formation involving ZMYND proteins.
- To identify potential targets for cancer diagnosis and therapy.
Main Methods:
- Literature review of studies on DEAF-1, ZMYND family, and associated genetic alterations.
- Analysis of gene expression, chromosomal translocations, copy number variations, and epigenetic modifications related to ZMYND proteins.
- Examination of the functional impact of ZMYND protein interactions and dysregulation on cell cycle and apoptosis.
Main Results:
- Chromosomal translocations forming fused genes (e.g., MTG8/ETO/ZMYND2) contribute to malignant transformation.
- Copy number variations (CNV) of BS69/ZMYND11 and hypermethylation of BLU/ZMYND10 are observed in malignancies.
- Fusion with RUNX1 disrupts MTG8/ZMYND2 co-repressor binding; BLU/ZMYND10 silencing affects cell cycle and apoptosis.
Conclusions:
- ZMYND proteins are crucial in regulating fundamental cellular processes like cell cycle and apoptosis.
- Alterations in ZMYND genes and their expression are linked to cancer development.
- Further research into ZMYND proteins can improve early tumor detection and therapeutic strategies.
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