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Title 

Positive regulation of apoptosis signal-regulating kinase 1 by hD53L1

Authors 

Sayeon ChoHyung Mun KoJung Min KimJung A LeeJae Eun ParkMi Sun JangSung Goo ParkDo Hee LeeSeong Eon RyuByoung Chul Park

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2004

Citation 

Journal of Biological Chemistry, vol. 279, no. 16, pp. 16050-16056

Keywords 

kinase activitysignal-regulating enzymesapoptosis signal regulating kinase 1protein d53l1stress activated protein kinaseapoptosisenzyme regulationsignal transductionupregulationadaptor proteins, signal transducing

Abstract 

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase family member that plays a central role in cytokine- and stress-induced apoptosis by activating c-Jun N-terminal kinase and p38 signaling cascades. ASK1-induced apoptotic activity is up-regulated by two cellular factors, Daxx and TRAF2, through direct protein-protein interactions. Daxx and TRAF2 are death receptor-associated proteins in Fas and tumor necrosis factor-α pathways, respectively. Recent studies suggest that calcium signaling may regulate ASK1 pathway. Here we report that human D53L1, a member of the tumor protein D52 family involved in cell proliferation and calcium signaling, up-regulates the ASK1-induced apoptosis. The human D53L1 physically interacts with the C-terminal regulatory domain of ASK1 and promotes ASK1-induced apoptotic activity by activating caspase signaling in mammalian cells. In luciferase reporter assays, hD53L1 activates c-Jun N-terminal kinase-mediated transactivation in the presence of ASK1. Expression of hD53L1 enhances autophosphorylation and kinase activity of ASK1 but has no effect on ASK1 oligomerization that is necessary for kinase activity and on binding of ASK1 to MKK6, a downstream factor of ASK1. Taken together, these results suggest that activation of ASK1 by hD53L1 may provide a novel mechanism for ASK1 regulation.

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M305758200

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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