Sam68 Is Required for Both NF-κB Activation and Apoptosis Signaling by the TNF Receptor

Ramakrishnan, Parameswaran; Baltimore, David

doi:10.1016/j.molcel.2011.05.007

Cited by 65 publications

(93 citation statements)

References 30 publications

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“…In contrast to this study, a recent report suggests that ubiquitinated RIP1 does not contribute to the recruitment of the TAK1 and IKK complexes to the TNF-RSC (63). cIAP1 is an E3 ligase for RIP1 (64).…”

Section: Discussioncontrasting

confidence: 99%

EGLN3 Inhibition of NF-κB Is Mediated by Prolyl Hydroxylase-Independent Inhibition of IκB Kinase γ Ubiquitination

Taubman

2013

Molecular and Cellular Biology

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NF-B transcription factors are crucial regulators of inflammation, immunity, stress responses, and cell differentiation. Many studies have demonstrated that ubiquitination of IB kinase ␥ (IKK␥), a regulatory subunit of IKK, is instrumental in the activation of IKK and NF-B. We and others previously identified EGLN3, a member of a family of prolyl hydroxylases, as a negative regulator of the NF-B pathway. Here we report that EGLN3, but not EGLN1 or -2, interacts with and inhibits K63-linked ubiquitination of IKK␥. The effect appears to be related to inhibition of IKK␥ ubiquitination mediated by cIAP1 rather than to stimulation of IKK␥ deubiquitination by the deubiquitinases A20 and CYLD (cylindromatosis). EGLN3 does not affect the protein levels of cIAP1 or its E2 ubiquitin-conjugating enzymes UbcH5 and Ubc13. EGLN3 hydroxylase activity is not responsible for its effect on IKK␥ ubiquitination and NF-B signaling. Instead, interaction with IKK␥ is required for the ability of EGLN3 to inhibit IKK␥ ubiquitination and IKK-NF-B signaling. EGLN3 competes with cIAP1 for IKK␥ binding, leading to inhibition of cIAP1-IKK␥ interaction, IKK␥ ubiquitination, and IKK-NF-B signaling. This study provides novel insights into EGLN3 function and sheds new light on the regulation of IKK␥ ubiquitination and NF-B.

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Section: Discussioncontrasting

confidence: 99%

EGLN3 Inhibition of NF-κB Is Mediated by Prolyl Hydroxylase-Independent Inhibition of IκB Kinase γ Ubiquitination

Taubman

2013

Molecular and Cellular Biology

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“…Aliquots of the lysates were also analyzed by Western blotting. For analysis of TNF-␣-induced complex II, MEFs were treated with TNF-␣ (100 ng/ml) and cycloheximide (1 g/ml) for the times indicated in the figure legends, and FADD/caspase-8/RIP1 complex was isolated and analyzed as reported by Ramakrishnan and Baltimore (33).…”

Section: Generation Of Trim-27mentioning

confidence: 99%

Ubiquitination-Deubiquitination by the TRIM27-USP7 Complex Regulates Tumor Necrosis Factor Alpha-Induced Apoptosis

Zaman

Nomura

Takagi³

et al. 2013

Molecular and Cellular Biology

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bTumor necrosis factor alpha (TNF-␣) plays a role in apoptosis and proliferation in multiple types of cells, and defects in TNF-␣-induced apoptosis are associated with various autoimmune diseases. Here, we show that TRIM27, a tripartite motif (TRIM) protein containing RING finger, B-box, and coiled-coil domains, positively regulates TNF-␣-induced apoptosis. Trim27-deficient mice are resistant to TNF-␣-D-galactosamine-induced hepatocyte apoptosis. Trim27-deficient mouse embryonic fibroblasts (MEFs) are also resistant to TNF-␣-cycloheximide-induced apoptosis. TRIM27 forms a complex with and ubiquitinates the ubiquitin-specific protease USP7, which deubiquitinates receptor-interacting protein 1 (RIP1), resulting in the positive regulation of TNF-␣-induced apoptosis. Our findings indicate that the ubiquitination-deubiquitination cascade mediated by the TRIM27-USP7 complex plays an important role in TNF-␣-induced apoptosis.

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“…9 (HGF)/Met receptor, 17 leptin 18 and tumor necrosis factor (TNF) receptors. 19 Sam68 has also been shown to re-localize in the cytoplasm near the plasma membrane, where it functions to transport and regulate the translation of certain mRNAs. 20 In particular, in spermatocytes, Sam68 transits into the cytoplasm to regulate the polysomal recruitment of specific mRNAs.…”

Section: Sam68 and Alternative Splicingmentioning

confidence: 99%

Emerging roles for Sam68 in adipogenesis and neuronal development

Vogel

Richard

2012

RNA Biology

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Sam68 Is Required for Both NF-κB Activation and Apoptosis Signaling by the TNF Receptor

Cited by 65 publications

References 30 publications

EGLN3 Inhibition of NF-κB Is Mediated by Prolyl Hydroxylase-Independent Inhibition of IκB Kinase γ Ubiquitination

EGLN3 Inhibition of NF-κB Is Mediated by Prolyl Hydroxylase-Independent Inhibition of IκB Kinase γ Ubiquitination

Ubiquitination-Deubiquitination by the TRIM27-USP7 Complex Regulates Tumor Necrosis Factor Alpha-Induced Apoptosis

Emerging roles for Sam68 in adipogenesis and neuronal development

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