GCN5-dependent acetylation of HIV-1 integrase enhances viral integration

Terreni, Mariaelena; Liverani, Vania; Gutiérrez, María Inés; Primio, Cristina Di; Fenza, Armida Di; Tozzini, Valentina; Albanese, Alberto; Arosio, Daniele; Giacca, Mauro; Cereseto, Anna

doi:10.1186/1742-4690-6-s2-p20

Cited by 15 publications

(22 citation statements)

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“…Three lysine residues (K264, K266, and K273) in the C-terminal domain of IN were identified acetylation sites. Additionally, the HIV-1 protein Tat is acetylated at K28 by the p300/CBP-associated factor (PCAF), while K50 and K51 are substrates for p300/CBP and GCN5, thus further confirming the essential role of acetylation as a post-translational modification during Tat activation and viral integration [354,364].…”

Section: Hivmentioning

confidence: 84%

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The world of protein acetylation

Drazic

Myklebust

Ree

et al. 2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

659

532

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Acetylation is one of the major post-translational protein modifications in the cell, with manifold effects on the protein level as well as on the metabolome level. The acetyl group, donated by the metabolite acetyl-coenzyme A, can be co- or post-translationally attached to either the α-amino group of the N-terminus of proteins or to the ε-amino group of lysine residues. These reactions are catalyzed by various N-terminal and lysine acetyltransferases. In case of lysine acetylation, the reaction is enzymatically reversible via tightly regulated and metabolism-dependent mechanisms. The interplay between acetylation and deacetylation is crucial for many important cellular processes. In recent years, our understanding of protein acetylation has increased significantly by global proteomics analyses and in depth functional studies. This review gives a general overview of protein acetylation and the respective acetyltransferases, and focuses on the regulation of metabolic processes and physiological consequences that come along with protein acetylation.

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Section: Hivmentioning

confidence: 84%

“…Acetylation events are also important for retroviral pathogenesis as demonstrated with the human immunodeficiency virus (HIV-1) [363,364]. The viral IN protein integrate reverse transcribed HIV-1 DNA into the cellular genome, and is a substrate for p300-mediated acetylation.…”

Section: Hivmentioning

confidence: 99%

The world of protein acetylation

Drazic

Myklebust

Ree

et al. 2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

659

532

View full text Add to dashboard Cite

show abstract

“…IN has been found to be post-translationally modified by acetylation [96][97][98] even though so far no role has been ascribed to this modification in nuclear import. Recently, another modification of this viral factor has been reported: IN is phosphorylated in activated T lymphocytes by the cellular C jun N-terminal kinase (JNK) at Ser57 [99].…”

Section: Nuclear Import and Beyond: The Role Of Cellular Kinases In Hmentioning

confidence: 98%

Role of Phosphorylation in the Nuclear Biology of HIV-1

Francis

Primio²,

Allouch³

et al. 2011

CMC

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The central events of HIV-1 life cycle occur at the nuclear level where the viral genome is integrated into the host cellular DNA in order to be expressed and replicated. The viral pre-integration complexes (PICs) are actively transported in the nuclear compartment where integration occurs in specific regions of the cellular chromatin. Similar to all viruses, HIV-1 encodes for a limited number of proteins that are insufficient to produce new viral progenies. Several cellular pathways are thus hijacked by HIV-1 to efficiently complete the replication cycle. The majority of viral proteins are substrates for cellular kinases indicating a pivotal role of these cellular enzymes at multiple steps of the HIV-1 life cycle. The nuclear biology of the cell is highly controlled by kinases (nuclear transport, DNA replication, repair and transcription) and many of these kinases also sustain the viral nuclear events. This review summarizes our current knowledge on kinases that are involved in HIV-1 replication cycle at the nuclear level, both directly through their catalytic activity on viral proteins and indirectly being activated by the virus. Among viral proteins directly modified by kinases is integrase (IN) the factor that catalyzes the integration of HIV-1 in the cellular genome. Notably, this recent discovery may shed light onto mechanisms underlying the different susceptibility of the main cell types targeted by HIV-1 (CD-4+ T-cell) depending on their activation status. Alternatively, kinases may act indirectly such as in the case of DNA repair factors activated following HIV-1 infection and demonstrated to regulate the viral life cycle. Finally, inhibition of cellular kinases interacting with HIV-1 at the nuclear level has been shown to severely affect the viral replication cycle, thus suggesting potential new therapeutic approaches.

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“…The acetylation of its specific lysine residues is thought to be involved in the viral DNA integration process. 55 concentrations of crowding agents due to steric effects. 57 A similar approach applied to the FPs or a FP-protein construct would aid the interpretation of the fluorescence microscopy data.…”

Section: Multiscale Modeling Of Proteins Tozzinimentioning

confidence: 99%

Multiscale Modeling of Proteins

2009

Self Cite

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The activity within a living cell is based on a complex network of interactions among biomolecules, exchanging information and energy through biochemical processes. These events occur on different scales, from the nano- to the macroscale, spanning about 10 orders of magnitude in the space domain and 15 orders of magnitude in the time domain. Consequently, many different modeling techniques, each proper for a particular time or space scale, are commonly used. In addition, a single process often spans more than a single time or space scale. Thus, the necessity arises for combining the modeling techniques in multiscale approaches. In this Account, I first review the different modeling methods for bio-systems, from quantum mechanics to the coarse-grained and continuum-like descriptions, passing through the atomistic force field simulations. Special attention is devoted to their combination in different possible multiscale approaches and to the questions and problems related to their coherent matching in the space and time domains. These aspects are often considered secondary, but in fact, they have primary relevance when the aim is the coherent and complete description of bioprocesses. Subsequently, applications are illustrated by means of two paradigmatic examples: (i) the green fluorescent protein (GFP) family and (ii) the proteins involved in the human immunodeficiency virus (HIV) replication cycle. The GFPs are currently one of the most frequently used markers for monitoring protein trafficking within living cells; nanobiotechnology and cell biology strongly rely on their use in fluorescence microscopy techniques. A detailed knowledge of the actions of the virus-specific enzymes of HIV (specifically HIV protease and integrase) is necessary to study novel therapeutic strategies against this disease. Thus, the insight accumulated over years of intense study is an excellent framework for this Account. The foremost relevance of these two biomolecular systems was recently confirmed by the assignment of two of the Nobel prizes in 2008: in chemistry for the discovery of GFP and in medicine for the discovery of HIV. Accordingly, these proteins were studied with essentially all of the available modeling techniques, making them ideal examples for studying the details of multiscale approaches in protein modeling.

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GCN5-dependent acetylation of HIV-1 integrase enhances viral integration

Cited by 15 publications

References 0 publications

The world of protein acetylation

The world of protein acetylation

Role of Phosphorylation in the Nuclear Biology of HIV-1

Multiscale Modeling of Proteins

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