title: TXNIP interacts with hEcd to increase p53 stability and activity.
abstract: The p53 protein plays a central role in cell cycle arrest and apoptosis in response to diverse stress stimuli. Human ecdysoneless (hEcd) is known for its role in stabilizing the p53 protein level and increasing p53-mediated transcription. Here, we report that thioredoxin interacting protein (TXNIP), a member of the tumor suppressor family, interacts with hEcd and decreases MDM2-mediated p53 ubiquitination, leading to p53 stabilization and an increase in p53 activity. The ectopic overexpression of both TXNIP and Ecd increased actinomycin D-mediated cell death in MCF-7 cells, whereas knockdown of TXNIP and Ecd decreased cell death. These results show that TXNIP is a new regulator of the Ecd-MDM2-p53 loop.
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Suh
authors.forename: Sohyun
authors.initials: S
authors.lastname: Yun
authors.forename: Haeyoung
authors.initials: H
authors.lastname: Song
authors.forename: Haiyoung
authors.initials: H
authors.lastname: Jung
authors.forename: Young-Jun
authors.initials: YJ
authors.lastname: Park
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism*; D016923:Cell Death; D003609:Dactinomycin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C513410:ECD protein, human; C495901:TP53 protein, human; C486715:TXNIP protein, human; D016159:Tumor Suppressor Protein p53; D003609:Dactinomycin; D013879:Thioredoxins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Cell death; Mdm2; TRX; TXNIP; hEcd; human ecdysoneless; murine double minute-2; p53; thioredoxin; thioredoxin interacting protein