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NEDD4L limits cAMP signaling through ubiquitination of CREB‐regulated transcription coactivator 3
Kim, Yo‐,Han,Yoo, Hanju,Hong, A‐,Reum,Kwon, Minseo,Kang, Sang‐,Wook,Kim, Kyunggon,Song, Youngsup Federation of American Society for Experimental Bi 2018 The FASEB Journal Vol.32 No.7
<P>The transcription factor cAMP-responsive element-binding protein (CREB) is involved in a variety of physiologic processes. Although its activity appears to be largely correlated with its phosphorylation status, cAMP-mediated dephosphorylation and the subsequent nuclear migration of the CREB-regulated transcription factors (CRTCs) are required to stimulate CREB transcriptional activity. Among the 3 identified mammalian homologs of CRTCs, CRTC3 has been shown to be expressed predominantly in adipose tissues in response to catecholamine signals that regulate lipid metabolism. Here, we show that prolonged cAMP signaling down-regulates CRTC3 in a proteasome-dependent manner and that neural precursor cell-expressed developmentally down-regulated gene 4-like (NEDD4L), a specific ubiquitin ligase for CRTC3, is responsible for this process. By recognizing the PY motif of CRTC3, NEDD4L interacts with CRTC3 and promotes its polyubiquitination. Interaction between NEDD4L and CRTC3 is further boosted by cAMP signaling, and this enhanced interaction appears to be dependent on the cAMP-mediated phosphorylation of NEDD4L at the Ser448 site. Furthermore, we show that food withdrawal stimulates NEDD4L phosphorylation in mice, which then show a decrease of adipose tissue CRTC3 protein levels. Together, these results suggest that NEDD4L plays a key role in the feedback regulation of cAMP signaling by limiting CRTC3 protein levels.Kim, Y.-H., Yoo, H., Hong, A.-R., Kwon, M., Kang, S.-W., Kim, K., Song, Y. NEDD4L limits cAMP signaling through ubiquitination of CREB-regulated transcription coactivator 3.</P>
Kim Junsoo,Youn Daehwa,Choi Seunghoon,Lee Youn Woo,Sumberzul Dulguun,Yoon Jeongeun,Lee Hanju,Bae Jong Woo,Noh Hyuna,On Dain,Hong Seung-Min,An Se-Hee,Jang Hui Jeong,Kim Seo Yeon,Kim Young Been,Hwang Ji 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Translational regulation in tissue environments during in vivo viral pathogenesis has rarely been studied due to the lack of translatomes from virus-infected tissues, although a series of translatome studies using in vitro cultured cells with viral infection have been reported. In this study, we exploited tissue-optimized ribosome profiling (Ribo-seq) and severe-COVID-19 model mice to establish the first temporal translation profiles of virus and host genes in the lungs during SARS-CoV-2 pathogenesis. Our datasets revealed not only previously unknown targets of translation regulation in infected tissues but also hitherto unreported molecular signatures that contribute to tissue pathology after SARS-CoV-2 infection. Specifically, we observed gradual increases in pseudoribosomal ribonucleoprotein (RNP) interactions that partially overlapped the trails of ribosomes, being likely involved in impeding translation elongation. Contemporaneously developed ribosome heterogeneity with predominantly dysregulated 5 S rRNP association supported the malfunction of elongating ribosomes. Analyses of canonical Ribo-seq reads (ribosome footprints) highlighted two obstructive characteristics to host gene expression: ribosome stalling on codons within transmembrane domain-coding regions and compromised translation of immunity- and metabolism-related genes with upregulated transcription. Our findings collectively demonstrate that the abrogation of translation integrity may be one of the most critical factors contributing to pathogenesis after SARS-CoV-2 infection of tissues.
Sung Soo Kim,Hwang Kyung Kim,Hanju Kim,Woo Tak Lee,이은성,Kyung Taek Oh,Han-Gon Choi,윤유석 대한약학회 2021 Archives of Pharmacal Research Vol.44 No.2
Albumin nanoparticles have become an attractivecancer nanomedicine platform due to their pharmaceuticaladvantages. Recently, photothermal therapy has beenextensively applied to cancer treatment due to heat-inducedtumor ablation. Herein, we fabricated albumin nanoparticles(HSA-NPs) loaded with paclitaxel (PTX), indocyanine green(ICG; a hyperthermal agent) and hyaluronidase (HAase) thatbreaks down hyaluronan, a major component of the extracellularmatrix (ECM) in tumors. Synthesis was based on aslightly modifi ed nanoparticle albumin-bound (Nab™) technique. The prepared nanoparticles (PTX/ICG/HAase-HSANPs)had a spherical shape with an average size of ~ 110 nmand a zeta potential of ~ -30.4 mV. They displayed good colloidalstability and typical patterns of ICG, HSA and HAasein UV–VIS–NIR and circular dichroism spectroscopic analysis. PTX/ICG/HAase-HSA-NPs were found to have excellenthyperthermal eff ects in response to near-infrared laserirradiation (808 nm) (up to > 50 °C over 4 min). The hyperthermiaconducted by PTX/ICG/HAase-HSA-NPs resultedin signifi cant cytotoxicity to pancreatic AsPC-1 cells atboth severe (> 50 °C) and mild (41–42 °C) hyperthermal states in conjunction with the inherent cytotoxic activity ofpaclitaxel. Furthermore, the confocal images of AsPC-1 cellspheroids proved PTX/ICG/HAase-HSA-NPs were able topermeate deeply into the three-dimensional tumor tissuemimicry structure. Most of all, PTX/ICG/HAase-HSANPsmaintained all these physicochemical and anti-cancerproperties irrespective of the amount of embedded HAase(1–5 mg). Our results demonstrated that PTX/ICG/HAase-HSA-NPs are a promising hyperthermal/chemotherapeuticanticancer agent.