Interferon-stimulated Gene 15 (ISG15) and ISG15-linked Proteins Can Associate with Members of the Selective Autophagic Process, Histone Deacetylase 6 (HDAC6) and SQSTM1/p62

Nakashima, Hiroshi; Nguyen, Tran; Goins, William F.; Chiocca, E. Antonio

doi:10.1074/jbc.m114.593871

Cited by 86 publications

(88 citation statements)

References 42 publications

(47 reference statements)

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“…We therefore hypothesized that antiviral effectors directly modulate the autophagic machinery. In cancer cell lines, the ubiquitin-like molecule ISG15 (76) modifies beclin 1 (77) and can bind directly to p62 (78). We found that ISG15 colocalized with Ͼ70% of clusters (Fig.…”

Section: Hsv-1 Replication In Tg Neurons Induces Atypical Autophagic mentioning

confidence: 81%

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Herpes Simplex Virus and Interferon Signaling Induce Novel Autophagic Clusters in Sensory Neurons

Katzenell

Leib

2016

J Virol

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IMPORTANCEHerpes simplex virus type 1 (HSV-1) is a ubiquitous virus and a significant cause of morbidity and some mortality. It is the causative agent of benign cold sores, but it can also cause blindness and life-threatening encephalitis. The success of HSV-1 is largely due to its ability to establish lifelong latent infections in neurons and to occasionally reactivate. The exact mechanisms by which neurons defend against virus infection is poorly understood, but such defense is at least partially mediated by autophagy, an intracellular pathway by which pathogens and other unwanted cargoes are degraded. The study demonstrates and investigates a new autophagic structure that appears to be specific to the interaction between neurotropic herpesviruses and murine primary sensory neurons. This work may therefore have important implications for our understanding of latency and reactivation. Herpes simplex virus 1 (HSV-1) is a highly prevalent human pathogen that establishes lifelong infection in the neurons of sensory and autonomic ganglia (1, 2). Initial infection and lytic replication at mucosal sites are followed by infection of innervating axonal termini of sensory neurons. Virions then travel in a retrograde direction to the soma, where they may replicate or immediately establish latency, depending partly on the infected neuronal subtype (3). Virions resulting from periodic reactivation events travel in an anterograde direction along the axon, allowing reinfection of the oral epithelium, thereby facilitating viral shedding and host-to-host transmission (2).Innate immune responses are critical in controlling virulence of HSV-1 and many other viruses through a variety of antiviral pathways (4-12), and viruses have coevolved to counter these host responses (13)(14)(15)(16)(17)(18)(19)(20). Cells detect the presence of incoming virus through pattern recognition receptors (21, 22) that, in turn, lead to the activation of pivotal transcription factors such as IRF (5, 23) and NF-B (24). These factors subsequently induce the production of type I interferon (IFN), which drives IFN-stimulated gene (ISG) expression (25) through a JAK-STAT-dependent pathway (26,27). This further stimulates production of type I IFN and ISGs to establish an antiviral state that consists of transcriptional and translational arrest, cytokine production, and apoptosis (28,29).Defects in innate immunity are often associated with increased susceptibility to HSV infection in both mice and humans, with frequent neurological sequelae (8,12,(30)(31)(32). That said, the IFNdriven responses of neurons themselves are muted and atypical (12,33). Nondestructive clearance is especially critical for postmitotic adult neurons, a population of irreplaceable cells that is essential for both the success and survival of the host. Indeed, there is mounting evidence that neurons depend on autophagy rather than inflammatory or cell-destructive responses for the control of intracellular pathogens (34-37). Autophagy is a highly conserved response to starvation, during...

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Section: Hsv-1 Replication In Tg Neurons Induces Atypical Autophagic mentioning

confidence: 81%

“…Another line of investigation in our lab is driven by the fact that p62 self-oligomerizes, possibly promoting cluster formation (87). Alternatively, vesicle clustering may be promoted by innate mediator ISG15 (28,88,89) which decorates the clusters and is known to interact with beclin 1 and p62 (77,78).…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus and Interferon Signaling Induce Novel Autophagic Clusters in Sensory Neurons

Katzenell

Leib

2016

J Virol

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“…FAT10 has been shown to bind to and regulate the solubility of polyQ proteins, and localize to aggresomes upon proteasome inhibition [58,59]. ISG15 has recently been shown to bind to HDAC6 and p62, and to promote degradation of aggregated proteins via aggrephagy [60].…”

Section: Aggrephagymentioning

confidence: 99%

Ubiquitin-Dependent And Independent Signals In Selective Autophagy

Khaminets

Behl

Đikić

2016

Trends in Cell Biology

597

520

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“…Besides Ub-based selective autophagy, HDAC6 is associated with autophagic clearance of IFN-induced ISG15-conjugated proteins. HDAC6 and p62 independently bind ISG15 and facilitate the autophagosome/lysosome degradation of ISG15 conjugates (Nakashima et al 2015). The role of HDAC6 in the fusion event is to control acetylation of salt-inducible kinase 2 (SIK2).…”

Section: Possible Mechanisms Of Hdacs In Cancer Developmentmentioning

confidence: 99%

HDACs and HDAC Inhibitors in Cancer Development and Therapy

Seto

2016

Cold Spring Harb Perspect Med

920

765

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Over the last several decades, it has become clear that epigenetic abnormalities may be one of the hallmarks of cancer. Post-translational modifications of histones, for example, may play a crucial role in cancer development and progression by modulating gene transcription, chromatin remodeling and nuclear architecture. Histone acetylation, a well-studied post-translational histone modification, is controlled by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs). By removing acetyl groups, HDACs reverse chromatin acetylation and alter transcription of oncogenes and tumor suppressor genes. In addition, HDACs deacetylate numerous non-histone cellular substrates that govern a wide array of biological processes including cancer initiation and progression. This review will discuss the role of HDACs in cancer and the therapeutic potential of HDAC inhibitors (HDACi) as emerging drugs in cancer treatment.

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Interferon-stimulated Gene 15 (ISG15) and ISG15-linked Proteins Can Associate with Members of the Selective Autophagic Process, Histone Deacetylase 6 (HDAC6) and SQSTM1/p62

Cited by 86 publications

References 42 publications

Herpes Simplex Virus and Interferon Signaling Induce Novel Autophagic Clusters in Sensory Neurons

Herpes Simplex Virus and Interferon Signaling Induce Novel Autophagic Clusters in Sensory Neurons

Ubiquitin-Dependent And Independent Signals In Selective Autophagy

HDACs and HDAC Inhibitors in Cancer Development and Therapy

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