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Homer1 regulates the susceptibility to TRAIL |
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| Authors: | Jin Na Shin Sujan Piya Dai-Wu Seol Ae Ran Moon |
| Affiliation: | a Department of Biochemistry, Chosun University School of Medicine, 375 Seosuk-Dong, Dong-Gu, Gwangju, 501-759, Republic of Korea b Medical Science and Engineering Research Center for Resistant Cells, Chosun University School of Medicine, 375 Seosuk-Dong, Dong-Gu, Gwangju, 501-759, Republic of Korea c School of Life Science and Biotechnology, Korea University, Seoul 136-701, Republic of Korea d Department of Life Science, Kyungwon University, San 65, Bokjeong Dong, Soojeong Gu, Sungnam, 461-700, Republic of Korea e Korea Basic Science Institute Gwang-Ju center, Chonnam National University 300 Yongbong-Dong, Buk-Gu, Gwang-Ju, 500-757, Republic of Korea |
| Abstract: | TRAIL is an apoptotic cell death-inducing ligand that belongs to a TNF superfamily. To identify the regulators that govern the susceptibility to TRAIL, TRAIL-resistant HeLa (TR) cells were established by repeatedly treating HeLa cells with TRAIL. Here we showed that scaffolding protein Homer1 plays a decisive role in regulating the apoptotic susceptibility to TRAIL. TR cells showing the normal susceptibility to FasL and chemotherapeutic agent etoposide expressed the lower protein levels of Homer1 than parental HeLa cells. They showed the delayed activation of caspases-8, Bid cleavage and Bax translocation to mitochondria in response to TRAIL. Reconstitution of Homer1 expression in TR cells significantly restored the susceptibility to TRAIL. In addition, knock-down of Homer1 using interfering shRNA in parental HeLa cells lost the susceptibility to TRAIL. Together, our data indicate that Homer1 plays a critical role in determining the apoptotic susceptibility to TRAIL. |
| Keywords: | TRAIL, Tumor Necrosis Factor-related Apoptosis-inducing Ligands DR4/5, death receptor 4/5 TR, TRAIL resistant DISC, death-inducing signaling complex mGluRIs, metabotropic glutamate receptors |
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