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Familial Testicular Germ Cell Tumor
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Other chromosomal loci (e.g., 2q14.2, 3q26.2, 4q35.2, 7q36.3, 9p24.3, 10q26.13, 15q21.3, 15q22.31, 16q22.3, 19p12, and Xq28) may also play a possible role in TGCT tumorigenesis [21]. In addition, tripartite motif (TRIM) family proteins contain the RING finger domain, which mainly functions as E3 ubiquitin ligases, and modulates ubiquitination leading to degradation, activation, or functional modification of target proteins. Of the 70 known genes within the TRIM family, approximately 20 (including TRIM44) are associated with malignancies through their involvement in cell proliferation, migration, and anti-apoptosis [22–33].
The genetics of breast and ovarian cancer
Published in J. K. Cowell, Molecular Genetics of Cancer, 2003
Phillippa J. Neville, Sarah J. Morland, Susan A. J. Vaziri, Graham Casey
Both BRCA1 and BRCA2 are large genes. BRCA1 encodes a protein of 1863 amino acids, whereas BRCA2 encodes a protein of 3418 amino acids. BRCA1 and BRCA2 share little homology with each other or with other known genes. However, both genes contain recognizable structural motifs (Figure 2). BRCA1 contains an amino terminus RING zinc finger domain and two carboxyl terminus BRCT (BRCA1 carboxyl terminus) repeats (Callebaut and Mornon, 1997; Koonin et al., 1996; Paterson, 1998). The BRCT domain is a poorly conserved domain found in several proteins many of which are involved in DNA repair, such as RAD9 and XRCC1 (Callebaut and Mornon, 1997; Koonin et al., 1996). The protein BARD1 (BRCA1 -associated ring domain) has been shown to associate with the RING finger domain of BRCA1 (Wu et al., 1996). A conserved feature of BRCA2 is the presence of eight copies of a 30–80 amino acid repeat (BRC repeat) (Bignell et al., 1997; Bork et al., 1996).
Pathobiology and molecular basis of MALT lymphoma
Published in Franco Cavalli, Harald Stein, Emanuele Zucca, Extranodal Lymphomas, 2008
Francesco Bertoni, Randy D Gascoyne
The t(11;18)(q21;q21) translocation is the most common translocation, occurring in 15–40% of cases.3,7,12,14–18 It results in the reciprocal fusion of two genes, comprising the cellular inhibitor of apoptosis protein 2 (API2; official gene symbol is now BIRC3) on chromosome 11q21 with MALT1 on chromosome 18q21. The creation of a fusion protein encoded by API2/MALT1 on the derivative chromosome 11 is the key pathogenetic event. API2 belongs to the inhibitor of apoptosis proteins (IAP) family, characterized by the presence of one to three baculovirus IAP repeat (BIR) domains.19API2 contains three N-terminal BIR domains, a middle caspase recruitment domain (CARD), and a C-terminal zinc binding RING finger domain (Figure 8.2). MALT1, a paracaspase, is composed of an N-terminal Death Domain (DD), followed by two Ig-like C2 domains and a caspase-like domain. All the breakpoints in the API2 gene occur downstream of the third BIR domain but upstream of the C-terminal RING, with over 90% of them just proximal to the CARD domain. In contrast, the breakpoints involving the MALT1 gene are more variable, but always upstream of the caspase-like domain. Thus, the resulting fusion gene API2/MALT1 always includes the N-terminal region of API2 gene with three intact BIR domains and the C-terminal portion of the MALT1 gene containing an intact caspase-like domain. The specific selection of certain functional domains of API2 and MALT1 to form a fusion product strongly suggests the importance and synergy of these domains in oncogenic activities.20
The participation of non-canonical autophagic proteins in the autophagy process and their potential as therapeutic targets
Published in Expert Opinion on Therapeutic Targets, 2023
Yiming Yin, Yourong Zhou, Xiaochun Yang, Zhifei Xu, Bo Yang, Peihua Luo, Hao Yan, Qiaojun He
Aside from the above observations, the interaction with non-canonical autophagic proteins, and how this interaction affects the state of autophagy has provided another intriguing aspect of the regulation of autophagy. When encountering energy stress, the previously mentioned protein TRAF6 promotes the activation of ULK1 in complex with AMBRA to induce autophagy [155]. Cereblon (CRBN) is a component of an E3 ligase complex that was found to mediate autophagy in a TRAF6-dependent manner [196–198]. Studies have shown that CRBN could inhibit the ubiquitin ligase ability of TRAF6 to downregulate the ubiquitination of BECN1 and act as an autophagy inhibitor [198]. Peroxiredoxin 1 (PRDX1) is a member of PRDXs, which plays a significant role in maintaining intracellular redox balance by detoxifying peroxides [199,200]. PRDX1 can inhibit the ubiquitin-ligase ability of TRAF6 by interacting with the ring finger domain of TRAF6 and can therefore defect the ubiquitination of BENC1 to inhibit autophagy [201]. Future studies could focus on digging into the interaction between non-canonical autophagic proteins; this might widen the current understanding of autophagy.
LINC00313 alleviates osteoarthritis progression in mice through promoting TRAF1 promoter methylation and inhibiting the ASK1/JNK signaling pathway
Published in Immunopharmacology and Immunotoxicology, 2022
Hongyan Li, Qingpeng Wang, Dapeng Gong
Tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) is one of the members of the TRAF family. TRAF proteins serve as important intracellular signaling adapters in TNF receptor, Toll-like receptor (TLR), cytokine, and antigen receptor signaling pathways [10]. TRAF1 differs from other members of the TRAF family in lacking the really interesting new gene (RING) finger domain in the N‐terminal region required for nuclear factor kappa B (NF-κB) activation [11]. Studies have shown that TRAF1 is implicated in molecular events regulating immunity, inflammation, and cell death. An investigation of acute lung injury provided evidence that TRAF1 inhibition effectively protected LPS-induced acute lung injury against inflammation, apoptosis and oxidative stress through suppressing the c-Jun N-terminal kinase (JNK) signaling [12]. TRAF1 knockdown alleviated palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway [13]. Furthermore, increased serum level of TRAF1 is correlated with disease activity and autoantibodies in rheumatoid arthritis (RA) which may serve as a serologic inflammatory marker of disease progression in RA patients [14]. Interestingly, a genome-wide DNA methylation analysis of articular chondrocytes identified that TRAF1 was hypomethylated in OA chondrocytes and has a consistent correlation with mRNA expression, which suggests that epigenetic changes in the methylation status of TRAF1 contribute to the progression of OA [15]. However, the role of TRAF1 in the regulation of OA progression remains poorly understood.
Inhibition of TRIM14 protects cerebral ischemia/reperfusion injury through regulating NF-κB/NLRP3 pathway-mediated inflammation and apoptosis
Published in Journal of Receptors and Signal Transduction, 2022
Xianlong Xie, Fan Wang, Xiujuan Li
Tripartite motif (TRIM) family proteins are conserved evolutionarily, which have a ring finger domain, one or two B-box domains, and a related coiled-coil domain in the amino-terminal region [6]. TRIM protein is related to a variety of cellular processes, such as cell differentiation, proliferation, inflammation, apoptosis, and innate immunity [7,8]. Many proteins in this family play an important role in cerebral I/R injury. For example, knockdown of TRIM22 could reduce the apoptosis and inflammation induced by oxygen–glucose deprivation/reoxygenation by inhibiting the NF-κB/NLRP3 axis [9]. TRIM8 inhibitor could regulate NF-κB activation-related inflammation and cell apoptosis and thus inhibit I/R-mediated brain injury [10]. In hepatic I/R injury, the functional role of TRIM27-TGF-β-activated kinase 1-JNK/p38 signaling was also reported [11]. TRIM47 has been reported to be a key regulator of cerebral I/R injury by regulating cell apoptosis and inflammation [12]. However, the role of TRIM14 in cerebral I/R injury remains unclear.