1. Introduction
The concept of
2. CYLD cutaneous syndrome
A genome search using two FC families identified strong evidence for linkage to the locus on chromosome 16q12-q13 (Biggs et al., 1995). Subsequently, germline mutations in the tumor suppressor
3. The function of CYLD
In 2003, CYLD was shown as a deubiquitinating enzyme that negatively regulates nuclear factor-kappa B (NF-κB) activation (Brummelkamp et al., 2003; Kovalenko et al., 2003; Trompouki et al., 2003; Wilkinson, 2003). NF-κB is involved in controlling inflammation, the immune response, and apoptosis (Pasparakis, 2002). Nowadays, many different cellular functions have been ascribed to CYLD such as proliferation and cell cycle, Ca2+ channel signaling, survival and apoptosis, inflammation, T-cell development and activation, antiviral response, and spermatogenesis (Pasparakis, 2002).
CYLD contains three cytoskeleton-associated protein-glycine-rich (CAP-Gly) domains, two proline-rich motifs, a tumor necrosis factor-alpha (TNF-α) receptor-associated factor 2 (TRAF2) binding site, and ubiquitin-specific proteases (USP) domain responsible for its deubiquitinases (DUB) activity (Harhaj et al., 2011; Pasparakis, 2002). The first two CAP-Gly domains mediate binding to microtubules (Gao et al., 2008; Wickström et al., 2010), and the third CAP-Gly domain regulates NEMO interactions. NEMO (also known as IκB kinase gamma (IKKγ)) is the regulatory subunit of the IκB kinase (IKK) (Yoshida et al., 2011). IKK plays crucial role in activating NF-κB in response to various inflammatory stimuli (Zheng et al., 2011). TRAF2 regulates activation of the c-Jun N-terminal kinase (JNK)/c-Jun and the inhibitor of IKK/ NF-κB signaling cascades in response to TNF-α stimulation (Zhang et al., 2011).
4. Conclusion
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