Inhibition of androgen receptor activity by histone deacetylase 4 through receptor SUMOylation

Yang, Yaping; Tse, Anfernee; Li, P; Ma, Qiuping; Xiang, Shengyan; Nicosia, Santo V.; Seto, Edward; Zhang, X; Bai, Wenlong

doi:10.1038/onc.2010.600

Cited by 63 publications

(40 citation statements)

References 40 publications

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“…MTT Cytotoxicity Assay and Crystal Violet Staining-For MTT assay, cells were treated as indicated with TRAIL alone or pretreated with CT for 12 h, washed with PBS, and then treated with TRAIL for an additional 24 h. Then, the effects of CT on TRAIL-induced cytotoxicity were determined by the MTT uptake method (17). For crystal violet staining assay, cells (1 ϫ 10 5 ) were seeded in 60-mm dishes and then untreated or pretreated with CT for 12 h, washed with PBS, and then treated with TRAIL.…”

Section: Methodsmentioning

confidence: 99%

The Herbal Compound Cryptotanshinone Restores Sensitivity in Cancer Cells That Are Resistant to the Tumor Necrosis Factor-related Apoptosis-inducing Ligand

Tse

Chow

Cao

et al. 2013

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

The Herbal Compound Cryptotanshinone Restores Sensitivity in Cancer Cells That Are Resistant to the Tumor Necrosis Factor-related Apoptosis-inducing Ligand

Tse

Chow

Cao

et al. 2013

Journal of Biological Chemistry

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“…The genetic interaction between HDAC4 and Ubc9 was particularly interesting as a growing body of evidence indicates that SUMOylation is an important mechanism for regulation of neuronal protein activity (Henley et al 2014) and for regulation of memory formation (Yang et al 2012;Castro-Gomez et al 2013;Luo et al 2013;Chen et al 2014;Wang et al 2014;Drisaldi et al 2015). Moreover, HDAC4 has also been implicated as a putative E3 SUMO ligase, as its presence enhances the SUMOylation of MEF2 (Gregoire and Yang 2005;Zhao et al 2005) and of the androgen receptor (Yang et al 2011) in mammalian cells. To further explore the link between HDAC4 and SUMOylation, we investigated the interaction of HDAC4 with Ubc9 and other members of the SUMOylation machinery (Table 4).…”

Section: Hdac4 Interacts With the Sumoylation Machinerymentioning

confidence: 99%

Long-Term Memory inDrosophilaIs Influenced by Histone Deacetylase HDAC4 Interacting with SUMO-Conjugating Enzyme Ubc9

et al. 2016

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HDAC4 is a potent memory repressor with overexpression of wild type or a nuclear-restricted mutant resulting in memory deficits. Interestingly, reduction of HDAC4 also impairs memory via an as yet unknown mechanism. Although histone deacetylase family members are important mediators of epigenetic mechanisms in neurons, HDAC4 is predominantly cytoplasmic in the brain and there is increasing evidence for interactions with nonhistone proteins, suggesting HDAC4 has roles beyond transcriptional regulation.To that end, we performed a genetic interaction screen in Drosophila and identified 26 genes that interacted with HDAC4, including Ubc9, the sole SUMO E2-conjugating enzyme. RNA interference-induced reduction of Ubc9 in the adult brain impaired long-term memory in the courtship suppression assay, a Drosophila model of associative memory. We also demonstrate that HDAC4 and Ubc9 interact genetically during memory formation, opening new avenues for investigating the mechanisms through which HDAC4 regulates memory formation and other neurological processes.KEYWORDS histone deacetylase; SUMOylation; plasticity; neuron; memory T HE histone deacetylase HDAC4 is widely expressed in neurons throughout the brain (Darcy et al. 2010) and an increasing body of evidence indicates that HDAC4 plays important roles in neurological function Chen and Cepko 2009;Kim et al. 2012;Li et al. 2012;Sando et al. 2012;Sarkar et al. 2014). To that end, we recently demonstrated that in Drosophila, RNA interference (RNAi)-mediated knockdown of HDAC4 in the adult brain impairs long-term memory (LTM) in the courtship suppression assay, a model of associative memory (Fitzsimons et al. 2013). Similarly in humans, loss of one copy of HDAC4 correlates with brachydactyly mental retardation syndrome (BDMR), the neurological symptoms of which include intellectual disability and autism (Williams et al. 2010;Morris et al. 2012;Villavicencio-Lorini et al. 2013), and in mice, conditional knockout of HDAC4 in the brain results in impairments in hippocampal-dependent associative LTM . Despite this growing evidence of a critical role, the mechanism(s) through which HDAC4 positively influences LTM is unknown. This is in part because HDAC4 exists in both nuclear and cytoplasmic pools, and under basal conditions, the majority of HDAC4 is localized to the cytoplasm (Chawla et al. 2003;Darcy et al. 2010). Given the predominant nonnuclear localization, particularly the concentration of HDAC4 at dendritic spines (Darcy et al. 2010), we hypothesize that cytoplasmic HDAC4 is required in memory formation; however, the mechanisms through which HDAC4 acts outside the nucleus are unknown.The nuclear role of HDAC4 is less of an enigma. When in the nucleus, HDAC4 acts as a transcriptional repressor; although vertebrate HDAC4 is catalytically inactive as a histone deacetylase, rather it facilitates changes in gene expression through direct binding and inhibition of transcription factors such as MEF2 (Miska et al. 1999;Wang et al. 1999;Lu et al. 2000). As described abov...

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“…As HDAC4 is itself a target of sumoylation, it has been suggested that a sumoylation cascade may take place, yet a SUMO-deficient HDAC4 can still promote AR-Su (Yang et al 2011b).…”

Section: Ar-sumoylationmentioning

confidence: 99%

Regulation of the androgen receptor by post-translational modifications

Coffey

Robson

2012

Journal of Endocrinology

119

100

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The androgen receptor (AR) is a key molecule in prostate cancer and Kennedy's disease. Understanding the regulatory mechanisms of this steroid receptor is important in the development of potential therapies for these diseases. One layer of AR regulation is provided by post-translational modifications including phosphorylation, acetylation, sumoylation, ubiquitination and methylation. While these modifications have mostly been studied as individual events, it is becoming clear that these modifications can functionally interact with each other in a signalling pathway. In this review, the effects of all modifications are described with a focus on interplay between them and the functional consequences for the AR.

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Inhibition of androgen receptor activity by histone deacetylase 4 through receptor SUMOylation

Cited by 63 publications

References 40 publications

The Herbal Compound Cryptotanshinone Restores Sensitivity in Cancer Cells That Are Resistant to the Tumor Necrosis Factor-related Apoptosis-inducing Ligand

The Herbal Compound Cryptotanshinone Restores Sensitivity in Cancer Cells That Are Resistant to the Tumor Necrosis Factor-related Apoptosis-inducing Ligand

Long-Term Memory inDrosophilaIs Influenced by Histone Deacetylase HDAC4 Interacting with SUMO-Conjugating Enzyme Ubc9

Regulation of the androgen receptor by post-translational modifications

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