상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Positive regulation of apoptosis signal-regulating kinase 1 signaling by ZPR9 protein, a zinc finger protein

Authors 

H A SeongHaiyoung JungR ManoharanH Ha

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2011

Citation 

Journal of Biological Chemistry, vol. 286, no. 36, pp. 31123-31135

Keywords 

Cell cycleCellular responseComplex formationsDisulfide linkagesEctopic expressionsEmbryonic developmentInduced apoptosisKinase activityMurine proteinsNegative regulatorsOncogenesisPhysiological substrateTranscriptional activityWild typesZinc finger protein

Abstract 

A zinc finger protein, ZPR9, has been identified as a physiological substrate of murine protein serine/threonine kinase 38 (MPK38), which is involved in various cellular responses, including the cell cycle, apoptosis, embryonic development, and oncogenesis. Here, ZPR9 was found to physically interact with apoptosis signal-regulating kinase 1 (ASK1) through a disulfide linkage involving Cys 1351 and Cys 1360 of ASK1 and Cys 305 and Cys 308 of ZPR9. ASK1 directly phosphorylated ZPR9 at Ser 314and Thr 318, suggesting that ZPR9 can act as an ASK1 substrate. Ectopic expression of wild-type ZPR9, but not an S314A/T318A mutant, stimulated ASK1 kinase activity and positively regulated ASK1-mediated signaling to both JNK and p38 kinases by destabilizing complex formation between ASK1 and its negative regulators, Trx and 14-3-3, or by increasing complex formation between ASK1 and its substrate MKK3. ZPR9 functionally stimulated ASK1-induced AP-1 transcriptional activity as well as H 2O 2-mediated apoptosis in a phosphorylation-dependent manner. ASK1-mediated phosphorylation of ZPR9 at Ser 314 and Thr 318 was also responsible for ZPR9-induced apoptosis. Moreover, ZPR9 inhibited PDK1-mediated signaling through ASK1 activation. These results suggest that ZPR9 functions as a novel positive regulator of ASK1.

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M111.248674

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)