Functional interaction between hMYH and hTRADD in the TNF-α-mediated survival and death pathways of HeLa cells.
The tumor necrosis factor (TNF) signaling pathway is a classical immune system pathway that plays a key role in regulating cell survival and apoptosis. The TNF receptor-associated death domain (TRADD) protein is recruited to the death domain of TNF receptor 1 (TNFR1), where it interacts with TNF receptor-associated factor 2 (TRAF2) and receptor-interacting protein (RIP) for the induction of apoptosis, necrosis, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and mitogen-activated protein (MAP) kinase activation. In this study, we found that the human MutY homolog (hMYH) interacted with human TRADD (hTRADD) via the C-terminal domain of hMYH. Moreover, under conditions promoting TNF-α-induced cell death or survival in HeLa cells, this interaction was weakened or enhanced, respectively. The interaction between hMYH and hTRADD was important for signaling pathways mediated by TNF-α. Our results also suggested that the hTRADD-hMYH association was involved in the nuclear translocation of NFκB and formation of the TNFR1-TRADD complex. Thus, this study identified a novel mechanism through which the hMYH-hTRADD interaction may affect the TNF-α signaling pathway.


CONCLUSIONS
In HeLa cells, the hTRADD-hMYH interaction functioned in both cell survival and apoptosis pathways following TNF-α stimulation.
Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
An Hue
AH
Vy Tran
Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Soo-Hyun
SH
Hahm
Department of Advanced Technology Fusion, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Se Hee
SH
Han
Department of Applied Bioscience, College of Life Science, CHA University, Gyeonggi-do 463-836, Republic of Korea.
Ji Hyung
JH
Chung
Cornell University, Ithaca, NY 14850, USA.
Geon Tae
GT
Park
College of Global Integrated Studies, Division of Interdisciplinary Studies, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: yshan@konkuk.ac.kr.
Ye Sun
YS
Han
D017209:Apoptosis; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009336:Necrosis; D054730:Protein Interaction Domains and Motifs; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I; D053199:TNF Receptor-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
Death-inducing signaling complex; MutY homolog (MYH); NFκB nuclear translocation; TNFR-associated death domain (TRADD); Tumor necrosis factor alpha (TNF-α)