Isoform specific regulation of divalent metal (ion) transporter (DMT1) by proteasomal degradation.
Isoform specific regulation of divalent metal (ion) transporter (DMT1) by proteasomal degradation.
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DOI：
10.1007/s10534-012-9522-1
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发表时间：
2012-08
期刊：
影响因子：
3.5
通讯作者：
Garrick, Laura M.
中科院分区：
文献类型：
--
作者：
Garrick, Michael D.;Zhao, Lin;Roth, Jerome A.;Jiang, Houbo;Feng, Jian;Foot, Natalie J.;Dalton, Hazel;Kumar, Sharad;Garrick, Laura M.
关键词：
DMT1 is the major transporter for iron entrance into mammalian cells and iron exit from endosomes during the transferrin cycle. Four major mRNA isoforms correspond to 4 protein isoforms, differing at 5'/3' and N-/C- termini, respectively. Isoforms are designated 1A vs. 1B reflecting where transcription starts or +IRE vs. −IRE reflecting the presence / absence of an iron responsive element in the 3' end of the mRNA. These differences imply regulation at transcriptional and posttranscriptional levels. Many proteins are degraded by a ubiquitination-dependent mechanism. Two different ubiquitin ligases (E3s) appear to be involved in DMT1 ubiquitination: Parkin or Nedd4 family E3s which often utilize Nedd4 family interacting protein-1 and -2 (Ndfip1 & 2) to ubiquitinate their substrate proteins. Prior data suggest that parkin ubiquitinates 1B DMT1 but not 1A DMT1 while Nedd4/Ndfips ligate ubiquitin to DMT1 in the duodenum where 1A/+IRE DMT1 predominates. Our assay for whether these systems target DMT1 depends on two HEK293 cell lines that express permanently transfected 1A/+IRE DMT1 or 1B/−IRE DMT1 after induction by doxycycline. Transient transfection with a parkin construct before induction diminishes 1B/−IRE DMT1 detected by immune-blots but not 1A/+IRE DMT1. Mutant parkin serves as a control that does not affect DMT1 levels. Thus DMT1 regulation in an isoform specific fashion can occur by ubiquitination and the events involved have implications for DMT1 function and disease processes.
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影响因子：
29
作者：
Shah YM;Matsubara T;Ito S;Yim SH;Gonzalez FJ
通讯作者：
Gonzalez FJ
影响因子：
5.8
作者：
Lis, A;Paradkar, PN;Roth, JA
通讯作者：
Roth, JA
影响因子：
29
作者：
Galy, Bruno;Ferring-Appel, Dunja;Hentze, Matthias W.
通讯作者：
Hentze, Matthias W.
影响因子：
20.3
作者：
Foot, Natalie J.;Leong, Yew Ann;Kumar, Sharad
通讯作者：
Kumar, Sharad
DOI：
10.1073/pnas.192423399
发表时间：
2002-09-17
影响因子：
11.1
作者：
Hubert, N;Hentze, MW
通讯作者：
Hentze, MW