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Gene & Protein in Disease Comprehensive analysis of ZNF521/Zfp521

neural differentiation. Forced expression of p300 alone promoter region leads to Zfp521 over expression, leading to
15
stimulates neural differentiation in ESCs. However, the leukemia. 46,76 Furthermore, there is a connection between
neural facilitation effect of p300 was not observed in ZNF521 and human leukemia. 76,77 Translocations that
Zfp521-null ESCs, suggesting that Zfp521 is required for engender ZNF521 and PAX5 chimeric fusion proteins were
21
p300 to boost neural differentiation (Figure 6). In ESCs, identified in childhood ALL, and ZNF521 overexpression
Zfp521 binds to p300 through the N-terminal ZF1-ZF8 was observed in patients with translocations that generate
to activate early neural genes, including Sox1, Sox3, Pax6, the E2A-HLF fusion protein. 4,39,76
and N-cadherin (Ncad, also known as Cdh2) and trigger Human ovarian cancer (hOC) is a highly invasive,
neural differentiation 15,21,73 (Figure 6). Loss of ZF9-30 in advanced female tumor. Recent studies have revealed
the Zfp521 protein leads to a loss of its neuropathizing that the occurrence and development of hOC involve
activity. 6,21 various molecular pathways, including NRF2 (nuclear
Neural stem cells (NSCs) can be generated from the factor erythroid 2-related factor 2) and NOTCH signaling
78
abundant astrocytes present in the mammalian brain pathways. The expression of ZNF521 is positively
and are more likely to reprogram astrocytes into neural correlated to NRF2-NOTCH signaling. 78-80
lineages. The over expression of Zfp521 in astrocytes
causes the conversion of these cells into proliferating 6. Conclusion
neural progenitor cells named INSCs. Adult mouse brain- In this review, we delved into the current research on
derived astrocytes can be converted to self-renewing ZNF521/ZFP521, focusing on its structure, function,
INSCs expressing relevant markers by Zfp521. These regulation, differentiation, and related diseases. We
suggest that Zfp521 is able to induce the transformation provided a detailed overview of ZNF521/ZFP521’s
of brain-derived astrocytes into INSCs in adult mice. 16,17,73 role in cell differentiation, its molecular mechanisms
As previously reported, apoptosis and senescence do not in differentiation-related diseases, and its interactions
increase with the passage of the INSCs, and these INSCs with ZNF423 and EBF1. ZNF521/ZFP521 is a stem cell-
have the potential to differentiate into neurons, astrocytes, related transcriptional cofactor with recognized regulatory
and oligodendrocytes. In summary, Zfp521 is sufficient to functions in hematopoiesis, mesenchyme, and immature
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convert adult mouse brain-derived astrocytes into iNSCs, regions of the nervous system, and it is also closely related
17
and forced expression of Zfp521 enables astrocytes to to the occurrence of leukemia, hOC, and OA.
overcome epigenetic barriers and transform into neural
stem cells even after CNS damage. 73 Acknowledgments
None.
5. Disease and treatment

First, the expression of E2A-HLF and Zfp521 enhances Funding
the proliferation of B progenitor cells, suggesting that their This work was supported by the Program for Science
co-expression synergistically promotes the occurrence and Technology Development in Henan Province
of B leukemia. 4,19,37,39,46 Therefore, it can be assumed that (No. 242102311227) and the Innovation Project for
ZNF521 plays an important role in the leukemia process College Students of Henan University (No. 20237003002,
of acute lymphoblastic leukemia (ALL). 1,74-76 The effect of 20237003003, and 202310475091).
Zfp521 on leukemia is closely related to the differentiation
of B cells. 12,23,39,46 For example, in cultured hematopoietic Conflict of interest
progenitor cells, the knockout of the Zfp521 gene can The authors declare that they have no conflicts of interest.
increase B-cell differentiation and the total number of
cultured cells. 12,39 Zfp521 may cooperate with tumor Author contributions
lesions to promote B-ALL development, possibly by Conceptualization: Yang An
inhibiting EBF1, thereby disrupting the functional Methodology: Tiantian Sun, Xu Han, Kangxu Chen
network governing normal B cell differentiation. In Software: Mengjie Tu, Jiayang Han, Binbin Zhao
5
addition, Zfp521 inhibits erythroid differentiation of Validation: Tiantian Sun, Xu Han, Kangxu Chen
leukemia cell lines by directly binding to GATA-1 and Formal analysis: Jialin Wu, Guangchao Liu, Kaifeng Zhang
inhibiting its activity. 3,6,23,29,74,75
Investigation: Jialin Wu, Guangchao Liu, Kaifeng Zhang
As widely acknowledged, the occurrence of tumors is Data curation: Mengjie Tu, Jiayang Han, Binbin Zhao
often linked to proto-oncogenes. Thus, Zfp521 is a B-cell Visualization: Man Yue, Mengwen Hou
proto-oncogene. The insertion of a retrovirus in its Project administration: Yang An
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Volume 3 Issue 3 (2024) 9 doi: 10.36922/gpd.3260