Signaling through the P38 and ERK pathways: a common link between HIV replication and the immune response

Furler, Robert L.; Uíttenbogaart, Christel H.

doi:10.1007/s12026-010-8170-1

Cited by 66 publications

(67 citation statements)

References 80 publications

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“…We infer that the preferential binding of the HIV-1 envelope glycoprotein gp120 to 6-O-sulfated groups over 2-O-sulfated groups on syndecans (47) may further delay endocytosis (43), thereby favoring infectious entry via fusion with cellular rafts. Moreover, ligand binding to syndecan-1 activates ERK, and ERK activation has been shown to facilitate HIV-1 infectivity and the assembly and release of new virions (51,52).…”

Section: Discussionmentioning

confidence: 99%

Molecular Mediators for Raft-dependent Endocytosis of Syndecan-1, a Highly Conserved, Multifunctional Receptor

Chen

Williams

2013

Journal of Biological Chemistry

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Background: Endocytosis via rafts remains incompletely characterized. Results: Raft-dependent endocytosis of syndecan-1 occurs in two phases, each requiring a kinase and a corresponding cytoskeletal partner. Each phase depends on MKKK, a novel, conserved motif within syndecan-1. Conclusion: These findings demonstrate the molecular choreography behind endocytosis of a raft-dependent receptor. Significance: Syndecans mediate uptake of biologically and medically important ligands.

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Section: Discussionmentioning

confidence: 99%

Molecular Mediators for Raft-dependent Endocytosis of Syndecan-1, a Highly Conserved, Multifunctional Receptor

Chen

Williams

2013

Journal of Biological Chemistry

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“…In addition, studies have shown that inhibition of HIV expression by nuclear receptors correlates with NCoR binding the LTR (38) and that HDAC3 is critical for repressing HIV transcription (35,36). NCoR1 enhances HDAC3 activity, whereas GPS2 has been reported to inhibit Ras/MAPK signaling (24), which activates HIV transcription (62,63). Therefore, recruitment of this complex to the HIV LTR would repress HIV transcription by altering chromatin as well as compromising signals necessary for efficient transcription.…”

Section: Discussionmentioning

confidence: 99%

Negative Elongation Factor (NELF) Coordinates RNA Polymerase II Pausing, Premature Termination, and Chromatin Remodeling to Regulate HIV Transcription

Natarajan

Lester

Lee

et al. 2013

Journal of Biological Chemistry

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Background: Multiple mechanisms contribute to HIV latency, including NELF-mediated RNA polymerase II (RNAP II) pausing. Results: Paused RNAP II recruits a transcription termination factor and a transcriptional corepressor complex to the HIV promoter. Conclusion: Paused RNAP II couples premature transcription termination and chromatin remodeling to maintain HIV latency. Significance: Paused RNAP II may be targeted to purge latent HIV infection.

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“…An important intracellular arm of the TCR response is regulated by the N-Ras GTPase that is activated at Golgi membranes downstream of Lck. [5][6][7][8][9] T-cell activation is thought to be beneficial to HIV-1 because it allows transcriptional activation of latent provirus and progression of the life cycle. However, activation-induced cell death after TCR engagement runs the risk of limiting the lifespan of productively infected cells and thus the amount of viral progeny produced.…”

mentioning

confidence: 99%

HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network–associated Lck signaling

Pan

Rudolph

Abraham

et al. 2012

Blood

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IntroductionReplication of HIV-1 in primary human T lymphocytes is tightly coupled to their activation state. Whereas HIV-1 undergoes early replication events in quiescent CD4 ϩ T lymphocytes, subsequent steps in the viral life cycle require cell activation. 1 T lymphocyte activation is primarily governed by signaling through the TCR complex after engagement in a tight contact with APCs; this is referred to as the immunological synapse (IS).TCR engagement by specific MHC-presented peptides launches highly dynamic and coordinated transport events that recruit specific factors to the IS and exclude others from it. This signal initiation triggers a broad cascade of downstream signaling that include dynamic F-actin remodeling at the IS, tyrosine phosphorylation, release of calcium flux, and activation of transcription. These events increase production of the T-cell survival cytokine IL-2 and are coordinated by the TCR proximal tyrosine kinase Lck, a master switch of TCR signaling. Immediately after TCR engagement, active Lck is recruited to the IS. 2-4 Whereas signal diversification and enhancement occur at the plasma membrane (PM), subsequent TCR signaling is compartmentalized and also occurs at intracellular membranes. An important intracellular arm of the TCR response is regulated by the N-Ras GTPase that is activated at Golgi membranes downstream of Lck. [5][6][7][8][9] T-cell activation is thought to be beneficial to HIV-1 because it allows transcriptional activation of latent provirus and progression of the life cycle. However, activation-induced cell death after TCR engagement runs the risk of limiting the lifespan of productively infected cells and thus the amount of viral progeny produced.Consequently, HIV-1 encodes gene products such as Nef to fine-tune the activation states of infected T lymphocytes. 10,11 Nef is a 25-to 34-kDa myristoylated accessory protein encoded by HIV-1, HIV-2, and SIV. Ex vivo, Nef enhances the single-round infectivity of virus particles and moderately accelerates virus spread over multiple rounds. 12 In vivo, Nef strongly boosts virus replication, particularly during primary infection, when the presence of Nef can elevate virus titers by more than 2 logs, and is critical for rapid disease progression. [13][14][15] This role of Nef as a pathogenicity factor is also revealed in transgenic mice, in which Nef expression induces AIDS-like depletion of CD4 ϩ T lymphocytes. 16 Delineating the mechanisms of Nef action has been hampered by the multitude of interactions with host T-cell proteins suggested to modulate various intracellular transport and signaling pathways. 17,18 This includes modulating exposure of cell-surface receptors such as MHC-I and II, CD4, and chemokine receptors to evade immune recognition and to prevent superinfection of infected cells, respectively (reviewed in Laguette et al 12 ). In addition, Nef affects the basal states of T-cell activation and the responsiveness of T lymphocytes to TCR signaling. [19][20][21][22] Initial studies with overexpression strategies ...

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Signaling through the P38 and ERK pathways: a common link between HIV replication and the immune response

Cited by 66 publications

References 80 publications

Molecular Mediators for Raft-dependent Endocytosis of Syndecan-1, a Highly Conserved, Multifunctional Receptor

Molecular Mediators for Raft-dependent Endocytosis of Syndecan-1, a Highly Conserved, Multifunctional Receptor

Negative Elongation Factor (NELF) Coordinates RNA Polymerase II Pausing, Premature Termination, and Chromatin Remodeling to Regulate HIV Transcription

HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network–associated Lck signaling

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