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Kim Y.,Korea University | Kim H.D.,Korea University | Youn B.,Pusan National University | Park Y.G.,Korea University | And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2013

Protein secretion is a general phenomenon by which cells communicate with the extracellular environment. Secretory proteins, including hormones, enzymes, toxins, and antimicrobial peptides have various functions in extracellular environments. Here, we determined that ribosomal protein S3 (rpS3) is homodimerized and secreted in several cancer cell lines such as HT1080 (human fibrosarcoma) and MPC11 (mouse plasmacytoma). Moreover, we found that the secreted rpS3 protein increased in doxorubicin-resistant MPC11 cells compared to that in MPC11 cells. In addition, we also detected that the level of secreted rpS3 increased in more malignant cells, which were established with continuous exposure of cigarette smoke condensate. These findings suggest that the secreted rpS3 protein is an indicator of malignant tumors. © 2013 Elsevier Inc.

Kim H.D.,Korea University | Jang C.-Y.,Sookmyung Womens University | Choe J.M.,Korea University | Choe J.M.,Korean Institute of Molecular Medicine and Nutrition | And 3 more authors.
Biochemical and Biophysical Research Communications | Year: 2012

It has been well known that three sentinel proteins - PERK, ATF6 and IRE1 - initiate the unfolded protein response (UPR) in the presence of misfolded or unfolded proteins in the ER. Recent studies have demonstrated that upregulation of UPR in cancer cells is required to survive and proliferate. Here, we showed that long exposure to 4-phenylbutyric acid (PBA), a chemical chaperone that can reduce retention of unfolded and misfolded proteins in ER, induced cellular senescence in cancer cells such as MCF7 and HT1080. In addition, we found that treatment with PBA activates Akt, which results in p21 WAF1 induction. Interestingly, the depletion of PERK but not ATF6 and IRE1 also induces cellular senescence, which was rescued by additional depletion of Akt. This suggests that Akt pathway is downstream of PERK in PBA induced cellular senescence. Taken together, these results show that PBA induces cellular senescence via activation of the Akt/p21 WAF1 pathway by PERK inhibition. © 2012 Elsevier Inc.

Kim H.D.,Korea University | Kim H.D.,Korean Institute of Molecular Medicine and Nutrition | Yu S.-J.,Korea University | Yu S.-J.,Korean Institute of Molecular Medicine and Nutrition | And 11 more authors.
Journal of Biological Chemistry | Year: 2013

Background:IL-4 can directly inhibit growth of several tumor cell types, but the molecular mechanism is not known. Results:IL-4 induces senescence by increasing p21 WAF1/CIP1 expression through STAT6 and p38 MAPK. Conclusion:STAT6 and p38 MAPK play important roles in senescence induction by IL-4. Significance:This is the first report of cellular senescence induction by IL-4 and the responsible mechanism. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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