A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense

@inproceedings{Tsichritzis2007ADO,
  title={A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense},
  author={Theodore Tsichritzis and Peer C Gaentzsch and Stylianos Kosmidis and Anthony E. Brown and Efthimios M. C. Skoulakis and Petros Ligoxygakis and George Mosialos},
  booktitle={Development},
  year={2007}
}
The cylindromatosis (CYLD) gene is mutated in human tumors of skin appendages. It encodes a deubiquitylating enzyme (CYLD) that is a negative regulator of the NF-κB and JNK signaling pathways, in vitro. However, the tissue-specific function and regulation of CYLD in vivo are poorly understood. We established a genetically tractable animal model to initiate a systematic investigation of these issues by characterizing an ortholog of CYLD in Drosophila. Drosophila CYLD is broadly expressed during… 
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Functional analysis of the C. elegans cyld-1 gene reveals extensive similarity with its human homolog
TLDR
The results demonstrate extensively overlapping functions between the HsCYLD and CeCY LD, which establish the C. elegans protein as a valuable model for the elucidation of the complex activity of the human tumor suppressor protein.
CYLD negatively regulates Hippo signaling by limiting Hpo phosphorylation in Drosophila.
Protein Phosphatase 4 Negatively Regulates the Immune Deficiency-NF-κB Pathway during the Drosophila Immune Response
TLDR
The results highlight an evolutionarily conserved function of PP4c in the regulation of NF-κB signaling from Drosophila to mammals and propose an interaction between PP4 and the IKK complex.
Verloren negatively regulates the expression of IMD pathway dependent antimicrobial peptides in Drosophila
TLDR
Velo is an additional new negative regulator of the IMD pathway, possibly acting in both the nucleus and cytoplasm, and observed from in vivo analysis that Velo knock-down flies exhibit significant upregulation of the AMP expression and reduced bacterial load.
Tumor suppressor CYLD: negative regulation of NF-κB signaling and more
  • G. Courtois
  • Biology
    Cellular and Molecular Life Sciences
  • 2007
TLDR
CYLD is a protein with tumor suppressor properties which was originally discovered associated with cylindromatosis, an inherited cancer exclusively affecting the folicullo-sebaceous-apocrine unit of the epidermis and which has also been shown to control other seemingly disparate cellular processes.
CYLD: a deubiquitination enzyme with multiple roles in cancer.
The post-translational modification of different proteins via direct ubiquitin attachment is important for various cellular processes. Dysregulation of components of the ubiqutin system have been…
dRYBP Contributes to the Negative Regulation of the Drosophila Imd Pathway
TLDR
The role of dRYBP in the regulation of the Imd signaling pathway is to function as a ubiquitin adaptor protein together with SKPA to promote SCF-dependent proteasomal degradation of Relish.
Cylindromatosis and the CYLD gene: new lessons on the molecular principles of epithelial growth control
  • R. Massoumi, R. Paus
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2007
TLDR
The histopathology and histogenesis of cylindromas, and the available genetic information on patients with these skin appendage tumors, are summarized, and it is argued that these recent insights into CYLD function and cylindroma pathogenesis may lead to the development of novel molecular strategies for cancer prevention and treatment.
Transcription factor zfh1 downregulates Drosophila Imd pathway.
Update of cylindromatosis gene (CYLD) mutations in Brooke‐Spiegler syndrome: novel insights into the role of deubiquitination in cell signaling
TLDR
New roles for CYLD in immunity, lipid metabolism, spermatogenesis, osteoclastogenesis, antimicrobial defense, and inflammation are revealed using animal models of Brooke‐Spiegler syndrome.
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References

SHOWING 1-10 OF 61 REFERENCES
Negative Regulation of JNK Signaling by the Tumor Suppressor CYLD*
TLDR
A critical role is reported for CYLD in negatively regulating the c-Jun NH2-terminal kinase (JNK) and a receptor-dependent role of CYLD is suggested in regulating the IκB kinase pathway.
The Tumor Suppressor CYLD Interacts with TRIP and Regulates Negatively Nuclear Factor κB Activation by Tumor Necrosis Factor
TLDR
Findings indicate that cylindromas arise through constitutive NF-κB activation leading to hyperproliferation and tumor growth.
Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-κB
TLDR
It is reported here that inhibition of one of these enzymes, the familial cylindromatosis tumour suppressor gene (CYLD), having no known function, enhances activation of the transcription factor NF-κB, and this effect can be relieved by aspirin derivatives that inhibit NF-σB activity.
Drosophila immune deficiency (IMD) is a death domain protein that activates antibacterial defense and can promote apoptosis.
Brummer lipase is an evolutionary conserved fat storage regulator in Drosophila.
CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members
TLDR
Results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-κB that is required for appropriate cellular homeostasis of skin appendages.
Mutations in the Drosophila dTAK1 gene reveal a conserved function for MAPKKKs in the control of rel/NF-kappaB-dependent innate immune responses.
TLDR
The genetic demonstration of dTAK1's role in the regulation of Drosophila antimicrobial peptide gene expression suggests an evolutionary conserved role for TAK1 in the activation of Rel/NF-kappaB-mediated host defense reactions.
The Role of Ubiquitination in Drosophila Innate Immunity*
TLDR
Surprisingly, it is found that the Drosophila caspase DREDD and its partner dFADD are required for the activation of DmIKK and JNK, in addition to their role in Relish cleavage, which reveals an evolutionarily conserved role of ubiquitination in IKK activation.
Inducible Expression of Double-Stranded RNA Reveals a Role for dFADD in the Regulation of the Antibacterial Response in Drosophila Adults
Control of Fat Storage by a Drosophila PAT Domain Protein
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