Human pancreas-specific protein disulfide isomerase homolog (PDIp) is an intracellular estrogen-binding protein that modulates estrogen levels and actions in target cells.
Human pancreas-specific protein disulfide isomerase homolog (PDIp) is an intracellular estrogen-binding protein that modulates estrogen levels and actions in target cells.
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DOI:
10.1016/j.jsbmb.2009.02.008
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发表时间:
2009-05
影响因子:
4.1
通讯作者:
Zhu, Bao Ting
中科院分区:
文献类型:
--
作者:
Fu, Xin-Miao;Zhu, Bao Ting
Earlier studies showed that protein disulfide isomerase (PDI), a well-known protein folding catalyst, can bind estrogens. Whether other PDI homologs can also bind estrogens, and if so, what are the biological functions of this unique property are not known at present and thus are the subject of our present investigation. Here we report that, of the six representative PDI homologs examined (human PDI, PDIp, ERp57, ERp72, PDIA6 and rat PDIr), only the human pancreas-specific PDI homolog (PDIp) had a similar binding affinity for radiolabeled 17β-estradiol (E2) as did PDI, with apparent Kd values of 1.5 ± 0.3 and 1.5 ± 0.2 μM, respectively. However, PDIp and PDI had distinctly different binding preference for several estrogen analogs. Moreover, we found that PDIp could serve as a high-capacity intracellular E2-binding protein and could modulate the intracellular concentrations of E2 in cultured mammalian cells as well as in human pancreatic tissue. The PDIp-bound E2 in a cell could be released following a drop in the extracellular E2 concentrations, and the released E2 could then augment estrogen receptor-mediated transcriptional activity. Notably, the estrogen receptors α and β were also found to be expressed in rodent and human pancreatic tissues where high levels of PDIp were detected. Altogether, these data show that, in addition to its well-documented function as a protein folding catalyst, PDIp can also serve as an effective modulator of the cellular levels and biological actions of endogenous estrogens in certain target sites (such as the pancreas) where estrogen receptors and PDIp are co-present.
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DOI:
10.1073/pnas.0831079100
发表时间:
2003-04-15
影响因子:
11.1
作者:
Li, L;Haynes, MP;Bender, JR
通讯作者:
Bender, JR
影响因子:
2.9
作者:
Lo, An-Chi;Soliman, Amr S.;Abbruzzese, James L.
通讯作者:
Abbruzzese, James L.
影响因子:
4.8
作者:
Dias-Gunasekara, S;Gubbens, J;Benham, AM
通讯作者:
Benham, AM
影响因子:
4.8
作者:
BEAUDOIN, AR;GRONDIN, G;GROSSMAN, A
通讯作者:
GROSSMAN, A
影响因子:
4.8
作者:
Fortunati, N;Fissore, F;Frairia, R
通讯作者:
Frairia, R