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Jung J.H.,Konkuk University | Lee S.-M.,Konkuk University | Bae S.,Konkuk University | Lee S.-J.,Hanyang University | And 4 more authors.
FEBS Letters | Year: 2010

Triad 1 (2 RING [really interesting new gene] fingers and DRIL [double RING finger linked] 1) is an E3 ligase that induces apoptosis and clonogenic inhibition in myeloid cells through Gfi-1 stabilization. Here we demonstrate that Triad 1 induces apoptosis in several cancer cell lines including MCF7, A549, U2OS, and HCT 116 p53+/+ cells via its RING ligase activity. Interestingly, in these cancer cells, Triad 1-induced apoptosis is not mediated by Gfi-1 stabilization but is instead p53-dependent. Moreover, Triad 1 promotes transactivation of p53. These results suggest that Triad 1 can induce apoptosis through its ligase activity via p53 activation. © 2010 Federation of European Biochemical Societies.


Bae S.,Konkuk University | Kim S.-Y.,Konkuk University | Jung J.H.,Konkuk University | Yoon Y.,Konkuk University | And 13 more authors.
Cell Research | Year: 2012

The serine/threonine kinase Akt functions in multiple cellular processes, including cell survival and tumor development. Studies of the mechanisms that negatively regulate Akt have focused on dephosphorylation-mediated inactivation. In this study, we identified a negative regulator of Akt, MULAN, which possesses both a RING finger domain and E3 ubiquitin ligase activity. Akt was found to directly interact with MULAN and to be ubiquitinated by MULAN in vitro and in vivo. Other molecular assays demonstrated that phosphorylated Akt is a substantive target for both interaction with MULAN and ubiquitination by MULAN. The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability. These data provide insight into the Akt ubiquitination signaling network. © 2012 IBCB, SIBS, CAS All rights reserved.


Bae S.,Konkuk University | Jung J.H.,Konkuk University | Jung J.H.,Harvard University | Kim K.,Konkuk University | And 7 more authors.
FEBS Letters | Year: 2012

Murine double minute (MDM2) is an E3 ligase that promotes ubiquitination and degradation of tumor suppressor protein 53 (p53). MDM2-mediated regulation of p53 has been investigated as a classical tumorigenesis pathway. Here, we describe TRIAD1 as a novel modulator of the p53-MDM2 axis that induces p53 activation by inhibiting its regulation by MDM2. Ablation of TRIAD1 attenuates p53 levels activity upon DNA damage, whereas ectopic expression of TRIAD1 promotes p53 stability by inhibiting MDM2-mediated ubiquitination/degradation. Moreover, TRIAD1 binds to the C-terminus of p53 to promote its dissociation from MDM2. These results implicate TRIAD1 as a novel regulatory factor of p53-MDM2. Structured summary of protein interactions: p53 physically interacts with Mdm2 and Triad1 by anti tag coimmunoprecipitation (View Interaction: 1, 2, 3)Mdm2 physically interacts with Triad1 by anti tag coimmunoprecipitation (View interaction)p53 physically interacts with Mdm2 by anti tag coimmunoprecipitation (View interaction)Triad1 binds to p53 by pull down (View interaction)Mdm2 physically interacts with p53 by anti tag coimmunoprecipitation (View interaction)p53 physically interacts with Triad1 by anti tag coimmunoprecipitation (View interaction). © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


An I.-S.,Konkuk University | An S.,Konkuk University | Choe T.-B.,Konkuk University | Kang S.-M.,Konkuk University | And 5 more authors.
International Journal of Molecular Medicine | Year: 2012

This study aimed to evaluate the protective effects of Centella asiatica (C. asiatica) against ultraviolet B (UVB) damage in human keratinocytes using microRNA (miRNA) expression profiling analysis. Titrated extract of C. asiatica (TECA) demonstrated low cytotoxicity in normal human HaCaT keratinocytes only at low doses (<5 μg/ml). UVB (50 mJ/cm2) irradiation significantly decreased cell viability, and TECA treatment decreased the UVB toxicity. By using miRNA microarrays, we determined that 72 miRNAs had an altered expression following TECA treatment in UVB-irradiated keratinocytes (46 upregulated and 26 down-regulated). Using an miRNA target gene prediction tool and Gene Ontology (GO) analysis, we determined that miRNAs with altered expression were functionally related with the inhibition of apoptosis and cell proliferation. Overall, these results provide meaningful information to facilitate the understanding of TECA-mediated UVB protection in human keratinocytes.


Jung J.H.,Konkuk University | Bae S.,Konkuk University | Lee J.Y.,Konkuk University | Woo S.R.,Korea Institute of Radiological and Medical Sciences | And 10 more authors.
Cell Death and Differentiation | Year: 2011

Following DNA damage, p53 translocates to the cytoplasm and mitochondria, where it triggers transcription-independent apoptosis by binding to Bcl-2 family proteins. However, little is known about how this exonuclear function of p53 is regulated. Here, we identify and characterize a p53-interacting protein called Hades, an E3 ligase that interacts with p53 in the mitochondria. Hades reduces p53 stability via a mechanism that requires its RING-finger domain with ubiquitin ligase activity. Hades polyubiquitinates p53 in vitro independent of Mdm2 and targets a critical lysine residue in p53 (lysine 24) distinct from those targeted by Mdm2. Hades inhibits a p53-dependent mitochondrial cell death pathway by inhibiting p53 and Bcl-2 interactions. These findings show that Hades-mediated p53 ubiquitination is a novel mechanism for negatively regulating the exonuclear function of p53. © 2011 Macmillan Publishers Limited All rights reserved.

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