ZNF451

Last update 08 May 2025

Basic Info

Synonyms

Coactivator for steroid receptors, COASTER, dJ417I1.1

+ [6]

Introduction

E3 SUMO-protein ligase; has a preference for SUMO2 and SUMO3 and facilitates UBE2I/UBC9-mediated sumoylation of target proteins (PubMed:26524493, PubMed:26524494). Plays a role in protein SUMO2 modification in response to stress caused by DNA damage and by proteasome inhibitors (in vitro). Required for MCM4 sumoylation (By similarity). Has no activity with SUMO1 (PubMed:26524493). Preferentially transfers an additional SUMO2 chain onto the SUMO2 consensus site 'Lys-11' (PubMed:26524493). Negatively regulates transcriptional activation mediated by the SMAD4 complex in response to TGF-beta signaling. Inhibits EP300-mediated acetylation of histone H3 at 'Lys-9' (PubMed:24324267). Plays a role in regulating the transcription of AR targets (PubMed:18656483).

100 Clinical Results associated with ZNF451

100 Translational Medicine associated with ZNF451

0 Patents (Medical) associated with ZNF451

Literatures (Medical) associated with ZNF451

01 Jan 2024·Research

Single-Cell Spatial–Temporal Analysis ofZNF451in Mediating Drug Resistance and CD8⁺T Cell Dysfunction

Article

Author: Xiong, Jianbin ; Chen, Yifan ; Wu, Xin ; Wu, Yupeng ; Zhao, Qiangqiang ; Xiong, Jianbin ; Zhao, Qiangqiang ; Tang, Ning ; Wu, Xin ; Deng, Woding ; Deng, Zhixuan

Cisplatin is widely used to treat osteosarcoma, but recurrent cases often develop resistance, allowing the disease to progress and complicating clinical management. This study aimed to elucidate the immune microenvironment of osteosarcoma, providing insights into the mechanisms of recurrence and identifying potential therapeutic strategies. By analyzing multiple single-cell and bulk RNA-sequencing datasets, we discovered that the SUMOylation-related geneZNF451promotes osteosarcoma recurrence and alters its immune microenvironment.ZNF451was found to importantly enhance the growth, migration, and invasion of resistant cells while also reducing their sensitivity to cisplatin and lowering their apoptosis rate. Moreover, our data indicated thatZNF451plays a crucial role in bone resorption and epithelial–mesenchymal transition.ZNF451also regulates CD8+T cell function, leading to their exhaustion and transition to the CD8T.EXH state. Additionally, β-cryptoxanthin has been identified as a potential therapeutic agent that inhibits osteosarcoma progression by targetingZNF451. In summary, these findings highlight the critical role ofZNF451in promoting osteosarcoma progression and underscore its potential as a therapeutic target and biomarker for osteosarcoma.

08 Dec 2023·Science Advances

RAD54L2 counters TOP2-DNA adducts to promote genome stability

Article

Author: Serrano-Benitez, Almudena ; Voigt, Andrea ; Beli, Petra ; Morales-Juarez, David A ; Goh, Chen Gang ; Wang, Juanjuan ; Jackson, Stephen P ; Nitiss, Karin C ; Richards, Sean L ; Bowden, Anne Ramsay ; Gupta, Vipul ; Galanty, Yaron ; Thomas, John C ; Zagnoli-Vieira, Guido ; D'Alessandro, Giuseppina ; Nitiss, John L ; Belotserkovskaya, Rimma

The catalytic cycle of topoisomerase 2 (TOP2) enzymes proceeds via a transient DNA double-strand break (DSB) intermediate termed the TOP2 cleavage complex (TOP2cc), in which the TOP2 protein is covalently bound to DNA. Anticancer agents such as etoposide operate by stabilizing TOP2ccs, ultimately generating genotoxic TOP2-DNA protein cross-links that require processing and repair. Here, we identify RAD54 like 2 (RAD54L2) as a factor promoting TOP2cc resolution. We demonstrate that RAD54L2 acts through a novel mechanism together with zinc finger protein associated with tyrosyl-DNA phosphodiesterase 2 (TDP2) and TOP2 (ZATT/ZNF451) and independent of TDP2. Our work suggests a model wherein RAD54L2 recognizes sumoylated TOP2 and, using its ATPase activity, promotes TOP2cc resolution and prevents DSB exposure. These findings suggest RAD54L2-mediated TOP2cc resolution as a potential mechanism for cancer therapy resistance and highlight RAD54L2 as an attractive candidate for drug discovery.

08 Dec 2023·Science Advances

RAD54L2-mediated DNA damage avoidance pathway specifically preserves genome integrity in response to topoisomerase 2 poisons

Article

Author: Pommier, Yves ; Park, Jeong-Min ; Li, Siting ; Tang, Mengfan ; Su, Dan ; Zhu, Dandan ; Wang, Chao ; Yang, Chang ; Zhang, Huimin ; Yin, Ling ; Chen, Junjie ; Xiong, Yun ; Sun, Yilun ; Feng, Xu ; Srivastava, Mrinal ; Keast, Sarah ; Chen, Zhen ; Huang, Min

Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that are reversible but can be trapped by TOP2 poisons. Trapped TOP2ccs block transactions on DNA and generate genotoxic stress, which are the mechanisms of action of TOP2 poisons. How cells avoid TOP2cc accumulation remains largely unknown. In this study, we uncovered RAD54 like 2 (RAD54L2) as a key factor that mediates a TOP2-specific DNA damage avoidance pathway. RAD54L2 deficiency conferred unique sensitivity to treatment with TOP2 poisons. RAD54L2 interacted with TOP2A/TOP2B and ZATT/ZNF451 and promoted the turnover of TOP2 from DNA with or without TOP2 poisons. Additionally, inhibition of proteasome activity enhanced the chromatin binding of RAD54L2, which in turn led to the removal of TOP2 from chromatin. In conclusion, we propose that RAD54L2-mediated TOP2 turnover is critically important for the avoidance of potential TOP2-linked DNA damage under physiological conditions and in response to TOP2 poisons.

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ZNF451

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