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Beschreibung

RING-box protein 2 (UniProt: Q9UBF6, also known as Rbx2, CKII beta-binding protein 1, CKBBP1, RING finger protein 7, Regulator of cullins 2, Sensitive to apoptosis gene protein) is encoded by the RNF7 (also known as RBX2, ROC2, SAG) gene (Gene ID: 9616) in human. RNF7/RBX2 and RBX1 are members of RING components of Cullin-RING ligases that are required for their enzymatic activity. RBX1 is shown to be constitutively expressed and binds to CUL 1-4, however, RNF7/RBX2 is induced by stress and associates with CUL5 and CUL1. RNF7/RBX2 is expressed in heart, liver, skeletal muscle, and pancreas and is present in cytoplasm and in the nucleus. RNF7/RBX2 is reported to negatively modulate beta-TrCP1 levels by shortening its protein half-life by promoting its ubiquitylation via atypical K11-linkage. It can serve as an antioxidant when acting alone or as an E3 ligase when complexed with other components of E3 ubiquitin ligases. It also acts as a survival protein by inhibiting apoptosis induced by a variety of stresses. Overexpression of RNF7/RBX2 is shown to inhibit apoptosis induced by redox, nitric oxide, ischemia, heat shock, and neurotoxins, both in vivo and in vitro. Overexpression of RNF7/RBX2 is observed in multiple human primary tumor tissues and its silencing by siRNA does not affect normal cell growth, but inhibits growth of cancer cells, both in vitro and in vivo by induction of apoptosis. Its silencing is also reported to sensitize radioresistant H1299 and U87 cells to ionizing radiation. (Ref.: Kaung, P., et al. (2016). Sci. Rep. 6, 37441, Jia, L., et al. (2010). Clin Cancer Res, 16(3), 814-824, Tan, M., et al. (2010), Free Rad. Biol. Med. 49(6), 976-983).

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