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Role of NF-κB in Macrophage Activation
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
The promoter region of the IκBα gene has a functionally important κB site (75). Activation of NF-κB by PM A treatment of 70Z/3 cells results in IκBα gene transcription reach maximum levels by 1 hour followed by a steady decline (65,76). Newly synthesized IκBα may be transported to the nucleus and inhibit NF-κB DNA binding activity (77). This was suggested to be the mechanism to recycle the NF-κB/BκIα complex back to cytoplasm and to make cells capable to respond to further activation signals. Indeed, J774 cells do re-synthesize IκBα 30 minutes after LPS treatment. Cytosolic levels of IκBα appear to recover to prestimulation levels within 1 hour. However, the newly synthesized IκBα appears to remain in cytosol, as nuclear NF-κB proteins remain highly elevated (see Fig. 1). The IκBα protein appears to be inherently unstable and has been shown to have a short half-life (6,7,66). This rapid turnover of IκBα is likely to be mediated by the proteasome system. However, unlike signal-induced degradation of IκBα, basal turnover appears to require neither ubiquitination of amino-terminal signal response element or carboxy-terminal PEST sequence (78).
Letrozole promotes the expression of integrin αvβ3 and HOXA10 in endometrium of endometriosis
Published in Systems Biology in Reproductive Medicine, 2022
Jing Zhang, Lihui Wang, Chunyan Li, Hui Zhang, Rui Li, Mingjiang Li
Integrin αvβ3 is a cell-surface receptor for extracellular matrix proteins that play an important role in embryo implantation (Lessey et al. 1992; Lessey, Castelbaum et al. 1994). Its expression shows periodic changes, and the peak time is consistent with the implantation window (Tabibzadeh 1992; Lessey et al. 1994a). The expression of integrin αvβ3 is decreased in women with infertility and endometriosis (Lessey et al. 1994a). Estrogen treatment can down-regulate the expression of integrin αvβ3 (Somkuti et al. 1997). HOXA10, = upstream gene integrin αvβ3 (Zhu et al. 2013), is also highly expressed during the implantation window and is a marker of endometrial receptivity (Gui et al. 1999). Estrogen can stimulate the expression of HOXA10, both in the myometrium and the endometrium (Cermik et al. 2001). In endometriosis, calpain7 can down-regulate the expression of HOXA10 via the PEST sequence, and the expression of integrin αvβ3 is also reduced (Yan et al. 2018). In addition, the expression of HOXA10 is decreased in endometriosis due to promoter methylation (Lu et al. 2013).
PLK4: a link between centriole biogenesis and cancer
Published in Expert Opinion on Therapeutic Targets, 2018
Radhika Radha Maniswami, Seema Prashanth, Archana Venkataramana Karanth, Sindhu Koushik, Hemalatha Govindaraj, Ramesh Mullangi, Sriram Rajagopal, Sooriya Kumar Jegatheesan
PLK4 also differs from other PLKs due to the presence of three PEST sequences which are characteristic of proteins with short half-lives. PLK4 possesses a half-life between 2 and 3 h. These PEST domains are rich in proline (P), aspartate (D), glutamate (E), serine (S), and threonine (T) residues, flanked on either side by a basic aa. They play a key role in regulating protein stability and turnover rate. PLK4 contains one PEST region at the amino terminus and two sequences at the carboxy terminus [15,48,53]. The first PEST sequence conserved throughout evolution contains a multiphospho degron motif, known to exert a greater impact on regulating PLK4 stability than the other two sequences [48,49]. Phosphorylation of the S and T residues in the degron region creates a binding site for SCF/β-TRCP E3 ubiquitin ligase complex followed by ubiquitination and PLK4 degradation [54,55]. Deletion of the PEST regions significantly increased nondegradable PLK4 level in transfected cells indicating the role of PEST motifs as critical regulatory regions [49].