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Biomedical subjects

A Migliaccio

Publications and source records attributed to A Migliaccio.

44 records · Page 3Linked to original sources
PubMed1981

Dephosphorylation of oestradiol nuclear receptor in vitro. A hypothesis on the mechanism of action of non-steroidal anti-oestrogens.

We show that a mouse uterus nuclear phosphatase exists that is capable of inactivating nuclear oestrogen receptor complexed to oestradiol-17 beta in vitro but is ineffective when the receptor is complexed with the two non-steroidal anti-oestrogens, nafoxidine and tamoxifen. We suggest that the long half-life of the tamoxifen-receptor complex versus the short half-life of the oestradiol-receptor complex in uterine nuclei in vivo is the result of the ineffectiveness of the phosphatase in dephosphorylating the anti-oestrogen-receptor complex.

Animals↗
PubMed1981

Inactivation of oestrogen receptor in vitro by nuclear dephosphorylation.

1. Nuclei of the calf uterus are endowed with an activity inactivating crude oestrogen-receptor complex. This activity has been partially purified. It shows a very high affinity for the oestrogen-receptor complex (Km = 0.8 X 10(-9) mol of specific [3H]oestradiol-17 beta-binding sites/l) as well as for the oestrogen-free receptor (Km = 1.5 X 10(-9) mol of specific [3H]oestradiol-17 beta binding sites/l). 2. The nuclear receptor-inactivating activity is enhanced by dithiothreitol and inhibited by several phosphatase inhibitors as well as by 4-nitrophenyl phosphate, as well known phosphatase substrate. This inhibition shows that a dephosphorylation process is required for the receptor inactivation. 3. The purified nuclear activity also inactivates pure receptor and phosphatase inhibitors prevent this inactivation. From these observations it appears that receptor inactivation is due to a nuclear phosphatase directly acting on the oestrogen receptor. 4. The nuclear localization of the receptor-inactivating activity, its high affinity for specific oestrogen binding sites and, as previously reported, its presence only in oestrogen target tissues suggest that this activity is the same as that involved in the nuclear loss of the receptor observed in intact cells.

Animals↗