KDM5 demethylases and their role in cancer cell chemoresistance

Plch, Johana; Hraběta, Jan; Eckschlager, Tomáš

doi:10.1002/ijc.31881

Cited by 74 publications

(64 citation statements)

References 85 publications

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“…However, the extent to which any of these pathways contribute to the cognitive impairments observed in patients remains unknown. A similar deficit exists in our understanding of how the dysregulation of human KDM5 genes contributes to cancer (Blair et al, 2011;Plch et al, 2019). In contrast to intellectual disability, which is exclusively associated with loss-of-function mutations in KDM5 genes, malignancies have been associated with overexpression of KDM5A or KDM5B, either loss or gain of KDM5C, or loss of KDM5D.…”

Section: Introductionmentioning

confidence: 99%

The histone demethylase KDM5 controls developmental timing in Drosophila by promoting prothoracic gland endocycles

et al. 2019

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In Drosophila, the larval prothoracic gland integrates nutritional status with developmental signals to regulate growth and maturation through the secretion of the steroid hormone ecdysone. While the nutritional signals and cellular pathways that regulate prothoracic gland function are relatively well studied, the transcriptional regulators that orchestrate the activity of this tissue remain less characterized. Here, we show that lysine demethylase 5 (KDM5) is essential for prothoracic gland function. Indeed, restoring kdm5 expression only in the prothoracic gland in an otherwise kdm5 null mutant animal is sufficient to rescue both the larval developmental delay and the pupal lethality caused by loss of KDM5. Our studies show that KDM5 functions by promoting the endoreplication of prothoracic gland cells, a process that increases ploidy and is rate limiting for the expression of ecdysone biosynthetic genes. Molecularly, we show that KDM5 activates the expression of the receptor tyrosine kinase torso, which then promotes polyploidization and growth through activation of the MAPK signaling pathway. Taken together, our studies provide key insights into the biological processes regulated by KDM5 and expand our understanding of the transcriptional regulators that coordinate animal development.

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Section: Introductionmentioning

confidence: 99%

The histone demethylase KDM5 controls developmental timing in Drosophila by promoting prothoracic gland endocycles

et al. 2019

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“…Genes of KDM5A, and KDM5C code lysine-specific demethylase enzymes. KDM5A is mutated in acute myeloid leukemia [23] and plays a role in breast cancer formation [77,78]. KDM5C is mutated in renal carcinoma [23] and plays a role in acute myeloid leukemia [77].…”

Section: Different Histone Ptms Play Various Roles In Normal Physiolomentioning

confidence: 99%

Molecular Structure, Binding Affinity, and Biological Activity in the Epigenome

Zsidó

Hetényi

2020

IJMS

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Development of valid structure–activity relationships (SARs) is a key to the elucidation of pathomechanisms of epigenetic diseases and the development of efficient, new drugs. The present review is based on selected methodologies and applications supplying molecular structure, binding affinity and biological activity data for the development of new SARs. An emphasis is placed on emerging trends and permanent challenges of new discoveries of SARs in the context of proteins as epigenetic drug targets. The review gives a brief overview and classification of the molecular background of epigenetic changes, and surveys both experimental and theoretical approaches in the field. Besides the results of sophisticated, cutting edge techniques such as cryo-electron microscopy, protein crystallography, and isothermal titration calorimetry, examples of frequently used assays and fast screening techniques are also selected. The review features how different experimental methods and theoretical approaches complement each other and result in valid SARs of the epigenome.

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“…This is mostly due to modulation of cell cycle-related genes and the p53 pathway, as detailed below. KDM5B and KDM5A are highly expressed in cancer (65,66). However, only KDM5A has been shown to play a role in suppressing senescence during tumorigenesis.…”

Section: Jmjc Demethylases Affect Cell Cycle Regulatory Genes To Suppmentioning

confidence: 99%

Jumonji C Demethylases in Cellular Senescence

Leon

Aird

2018

Preprint

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Senescence is a stable cell cycle arrest that is either tumor suppressive or tumor promoting depending on context. Epigenetic changes such as histone methylation are known to affect both induction and suppression of senescence by altering expression of genes that regulate the cell cycle and the senescence-associated secretory phenotype. A conserved group of proteins containing a Jumonji C (JmjC) domain alter chromatin state, and therefore gene expression, by demethylating histones. Here, we will discuss what is currently known about JmjC demethylases in induction of senescence and how these enzymes suppress senescence to contribute to tumorigenesis.

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KDM5 demethylases and their role in cancer cell chemoresistance

Cited by 74 publications

References 85 publications

The histone demethylase KDM5 controls developmental timing in Drosophila by promoting prothoracic gland endocycles

The histone demethylase KDM5 controls developmental timing in Drosophila by promoting prothoracic gland endocycles

Molecular Structure, Binding Affinity, and Biological Activity in the Epigenome

Jumonji C Demethylases in Cellular Senescence

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