IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
UDP-Glc:glycoprotein glucosyltransferase isoforms are regulated by Progesterone through different mechanisms
Autor/es:
ACOSTA AG; MIRANDA S; OGARA MF; CASTRO OA; RODRIGUEZ-SEGUI S
Lugar:
San Martin
Reunión:
Simposio; GlycoAr; 2019
Institución organizadora:
UNSAM, CONICET, FIL,
Resumen:
UDP-Glc: glycoprotein glucosyltransferase isoforms are regulated by Progesterone through different mechanismsAcosta, A; Ogara, F; Rodriguez-Seguí, S; Miranda, S and Castro, OUDP-Glc: glycoprotein glucosyltransferase is the key component of the quality control mechanism of glycoprotein folding. In humans (HUGE) and mice (UGGT), two enzymatically active isoforms were described and in vitro studies have previously shown that they were differentially regulated by progesterone (P4). Public ChIP-seq datasets for P4 receptor (PR) in T47D human mammary cells showed that P4 binds to two response elements (HRE) in HUGT2 at 10-8 M, and not to HUGT1. The aim of this work was to gain insight into the mechanisms involved in the regulation of both isoforms by P4. First, we studied UGGTs expression (immunohistochemistry and western blot) and their transcripts (RT-qPCR) in mouse mammary gland during pregnancy. Second, we confirmed HUGTs expression in T47D cells (immunofluorescence) and analyzed their expression in presence of P4 (10-5 to 10-10M) and R5020 (10-7M and 10-8M) In the mammary gland, results showed that both UGGTs are expressed ubiquitously and peak in epithelial cells at day 15 of pregnancy. The mRNA level expression of uggt1 increases throughout pregnancy while that of uggt-2 shows an opposite pattern. In 24h T47D cell cultures, HUGT1 was upregulated (+75%) in the presence of P4 10-5M. In contrast, HUGT2 was downregulated either with P4 10-6M/10-7M. PR-ChIP experiments at 3 and 6h (P4 10-8M) were performed and confirmed that P4 binds to two different HRE in HUGT2. These results indicate that both enzymes are regulated by P4 through different mechanisms.