The PWWP domain binds to both histone and DNA of a nucleosome in a bivalent way. PWWP domain-containing proteins are involved in different biological processes, and their aberrant expression is implicated in various human diseases. Here, we discuss the recent developments and challenges in targeting the PWWP domain for therapeutic intervention.
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| http://dx.doi.org/10.1016/j.tips.2024.01.007 | DOI Listing |
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The Emerging Roles of the Stress Epigenetic Reader LEDGF/p75 in Cancer Biology and Therapy Resistance: Mechanisms and Targeting Opportunities.
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Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
The lens epithelium derived growth factor of 75 kD (LEDGF/p75) is a transcription co-activator and epigenetic reader that has emerged as a stress oncoprotein in multiple human cancers. Growing evidence indicates that it promotes tumor cell survival against certain therapeutic drugs. The amino (N)-terminal region of LEDGF/p75 contains a PWWP domain that reads methylated histone marks, critical for recognizing transcriptionally active chromatin sites.
View Article and Find Full Text PDFPWWP domain-containing protein Crf4-3 specifically modulates fungal azole susceptibility by regulating sterol C-14 demethylase ERG11.
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Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
The widespread use of azole antifungals in agriculture and clinical settings has led to serious drug resistance. Overexpression of the azole drug target 14α-demethylase ERG11 (CYP51) is the most common fungal resistance mechanism. However, the presence of additional regulatory proteins in the transcriptional response of is not yet fully elucidated.
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State Key Laboratory of Protein and Plant Gene Research, School of Advanced Agricultural Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, No.5 Yiheyuan Road, Haidian District, Beijing 100871, China.
PWWP-DOMAIN INTERACTOR OF POLYCOMBS (PWO) family proteins play a vital role in regulating plant development. However, the molecular mechanisms of how PWOs regulate chromatin structure is elusive. Our data show that the PWO1 binding sites are enriched with positive modifications but exclusive with H3K27me3.
View Article and Find Full Text PDFLEDGF interacts with the NID domain of MeCP2 and modulates MeCP2 condensates.
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KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, 3000 Leuven, Flanders, Belgium. Electronic address:
Article Synopsis
- MeCP2 is a protein that regulates gene expression and chromatin structure, with two main forms, E1 and E2, and its mutations are linked to Rett syndrome.
- The study investigates how MeCP2 interacts with LEDGF, a transcription regulator, highlighting that the interaction requires a specific domain in MeCP2.
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December 2024
Biocrystallography, KU Leuven, Leuven, Belgium. Electronic address:
Lens epithelium-derived growth factor p75 (LEDGF/p75), member of the hepatoma-derived growth-factor-related protein (HRP) family, is a transcriptional co-activator and involved in several pathologies including HIV infection and malignancies such as MLL-rearranged leukemia. LEDGF/p75 acts by tethering proteins to the chromatin through its integrase binding domain. This chromatin interaction occurs between the PWWP domain of LEDGF/p75 and nucleosomes carrying a di- or trimethylation mark on histone H3 Lys36 (H3K36me2/3).
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