Regulation of T cell development by the deubiquitinating enzyme CYLD

Reiley, William W.; Zhang, Minying; Jin, Wei; Losiewicz, Mandy; Donohue, Keri B.; Norbury, Christopher C.; Sun, Shao‐Cong

doi:10.1038/ni1315

Cited by 205 publications

(250 citation statements)

References 48 publications

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“…Loss of CYLD in cylindromatosis is associated with tumor development of hair follicles and sweat and scent glands, which is coincident with increased NF-kB signaling. CYLD has recently been shown to also be important for T-cell development and has been implicated to promote deubiquitination of the T-cell-specific tyrosine kinase Lck (Reiley et al, 2006). NF-kB-induced cell death has also been linked to increased expression of the pro-death factors B7-H1 (PCD ligand 1, pdcd1), which induces apoptosis of T lymphocytes (Dong et al, 2002;Yu et al, 2004;Lee et al, 2005), and caspase-11, which can activate the death effector caspase-3 (Kang et al, 2000;Schauvliege et al, 2002).…”

Section: Mechanisms Implicated In Nf-kb's Proapoptotic Activitymentioning

confidence: 99%

Current insights into the regulation of programmed cell death by NF-κB

et al. 2006

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Section: Mechanisms Implicated In Nf-kb's Proapoptotic Activitymentioning

confidence: 99%

Current insights into the regulation of programmed cell death by NF-κB

et al. 2006

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“…Therefore, the loss-of-function of CYLD may lead to persistent activation of NF-kB to promote the survival of cancer cells (Brummelkamp et al, 2003;Kovalenko et al, 2003;Trompouki et al, 2003). Three groups have recently reported the phenotypes of CYLD knockout mice, which surprisingly are not identical (Massoumi et al, 2006;Reiley et al, 2006;Zhang et al, 2006). Massoumi et al (2006) showed that CYLD-deficient mice are prone to chemical-induced skin cancer, owing, in part, to enhanced K63-polyubiquitination of BCL3, an IkB-like protein that functions as a transcriptional coactivator by forming a complex with the p50 or p52 subunit of NF-kB.…”

Section: Deubiquitination Enzymes Inhibit Tak1 and Ikkmentioning

confidence: 99%

Ubiquitin-mediated activation of TAK1 and IKK

2007

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Transforming growth factor b activated kinase-1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, has emerged as a key regulator of signal transduction cascades leading to the activation of the transcription factors nuclear factor-kappa B (NF-jB) and activator protein-1 (AP-1). Stimulation of cells with cytokines and microbial pathogens results in the activation of TAK1, which subsequently activates the I-kappa B kinase complex (IKK) and mitogen-activated protein (MAP) kinases, culminating in the activation of NF-jB and AP-1, respectively. Recent studies have shown that polyubiquitination of signalling proteins through lysine (Lys)-63-linked polyubiquitin chains plays an important role in the activation of TAK1 and IKK. Unlike Lys-48-linked polyubiquitination, which normally targets proteins for degradation by the proteasome, Lys-63-linked polyubiquitin chains act as scaffolds to assemble protein kinase complexes and mediate their activation through proteasome-independent mechanisms. The concept of ubiquitin-mediated activation of protein kinases is supported by the discoveries of ubiquitination and deubiquitination enzymes as well as ubiquitin-binding proteins that function upstream of TAK1 and IKK. Recent biochemical and genetic studies provide further insights into the mechanism and function of ubiquitin signalling and these advances will be the focus of this review.

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“…In this sense, it has been shown that CYLD-deficiency specifically affects the normal differentiation of T-cells at the level of DP to SP transition. 26 Despite we have demonstrated that reverting CYLD is sufficient to prevent T-ALL in mice, our previous screening shows that both A20 and CYLD are downregulated in T-ALL human samples. 15 These results indicate that A20 and CYLD might compensate each other in some situations or pathologies and require additional mechanisms to be inactivated.…”

confidence: 99%