Identification and characterization of an early estrogen-regulated RNA in cultured guinea-pig endometrial cells

Pellerin, Isabelle; Vuillermoz, Cécile; Jouvenot, Michèle; Ordener, Catherine; Royez, M.; G.L, Adessi

doi:10.1016/0303-7207(93)90161-c

Cited by 35 publications

(25 citation statements)

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“…The gabarapl1 gene was originally identified as an early oestrogen-regulated gene in cultured guinea-pig endometrial glandular epithelial cells (GECs) (Pellerin et al, 1993). The human gene was then characterised (GeneBank Accession No.…”

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High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

et al. 2010

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BACKGROUND: This study evaluates the relation of the early oestrogen-regulated gene gabarapl1 to cellular growth and its prognostic significance in breast adenocarcinoma. METHODS: First, the relation between GABARAPL1 expression and MCF-7 growth rate was analysed. Thereafter, by performing macroarray and reverse transcriptase quantitative-polymerase chain reaction (RT -qPCR) experiments, gabarapl1 expression was quantified in several histological breast tumour types and in a retrospective cohort of 265 breast cancers. RESULTS: GABARAPL1 overexpression inhibited MCF-7 growth rate and gabarapl1 expression was downregulated in breast tumours. Gabarapl1 mRNA levels were found to be significantly lower in tumours presenting a high histological grade, with a lymph nodepositive (pN þ ) and oestrogen and/or progesterone receptor-negative status. In univariate analysis, high gabarapl1 levels were associated with a lower risk of metastasis in all patients (hazard ratio (HR) 4.96), as well as in pN þ patients (HR 14.96). In multivariate analysis, gabarapl1 expression remained significant in all patients (HR 3.63), as well as in pN þ patients (HR 5.65). In univariate or multivariate analysis, gabarapl1 expression did not disclose any difference in metastasis risk in lymph node-negative patients. CONCLUSIONS: Our data show for the first time that the level of gabarapl1 mRNA expression in breast tumours is a good indicator of the risk of recurrence, specifically in pN þ patients.

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High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

et al. 2010

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“…In contrast to the first, second, and third intracellular loops of the hKOR, which are short and homologous to those of and ␦ opioid receptors, the C-tail of the hKOR is highly divergent (11) and thus was used as the bait. GEC1, an early estrogen-regulated gene (12), was one of the proteins identified in the screening. GEC1 cDNA was originally cloned in 1993 from guinea-pig endometrial glandular epithelial cells as an early estrogen-induced mRNA (12).…”

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“…GEC1, an early estrogen-regulated gene (12), was one of the proteins identified in the screening. GEC1 cDNA was originally cloned in 1993 from guinea-pig endometrial glandular epithelial cells as an early estrogen-induced mRNA (12). This protein was also named GABA A receptor-associated protein-like 1 (13) and Apg8L (14).…”

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GEC1 Interacts with the κ Opioid Receptor and Enhances Expression of the Receptor

Chen

et al. 2006

Journal of Biological Chemistry

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We identified a truncated form (38 -117) of GEC1 that interacts with the C-tail of the human opioid receptor (hKOR) by yeast two-hybrid screening. GEC1-(38 -117) did not interact with the C-tail of the or ␦ opioid receptors. GEC1, a 117-amino acid protein (Pellerin, I., Vuillermoz, C., Jouvenot, M., Ordener, C., Royez, M., and Adessi, G. L. (1993) Mol. Cell Endocrinol. 90, R17-R21), is highly homologous to GABARAP, GATE-16, and Apg8/aut7, all members of the microtubule associated protein (MAP) family. In pull-down assays, GST-GEC1 interacted directly with the hKOR C-tail, full-length hKOR, and tubulin. When expressed in Chinese hamster ovary (CHO) cells, GEC1 co-immunoprecipitated with FLAG-hKOR. Expression of GEC1 greatly increased total and cellsurface KOR but not or ␦ opioid receptors. GEC1 expression slightly reduced U50,488H-promoted down-regulation, without affecting ligand binding affinity, receptor-G protein coupling, or U50,488H-induced desensitization and internalization. HA-GEC1 expressed in CHO cells was localized in the Golgi apparatus and endoplasmic reticulum (ER). When cells were pulsed with [ 35 S]Met/ Cys, GEC1 expression enhanced the level of the mature form (55-kDa band) of FLAG-hKOR at 4, 8, and 22 h after pulse without affecting the precursors (39-and 45-kDa bands), indicating that GEC1 facilitates trafficking of FLAG-hKOR from the ER/Golgi to plasma membranes. GEC1 interacted with N-ethylmaleimide-sensitive factor (NSF) in pull-down assays and co-immunoprecipitated with NSF in rat brain extracts. The interaction with NSF may contribute to GEC1 effects. This is the first report on biological functions of GEC1 and the first demonstration that a GPCR interacts with a protein of the MAP family. The interaction is important for trafficking of the receptor in the biosynthesis pathway.Activation of opioid receptors in vivo produces many effects, including antinociception (1, 2), psychotomimesis (2, 3), and water diuresis (1, 2). At the cellular level, opioid receptors are coupled through pertussis toxin-sensitive G proteins to affect a variety of effectors, which include adenylate cyclase, potassium, and calcium channel and the p42/ p44 mitogen-activated protein kinase (for a review, see Ref. 5). Following cloning of the ␦ opioid receptor, the opioid receptor has been cloned from several species (for a review, see Ref. 6). The opioid receptors belong to the rhodopsin sub-family of the G protein-coupled receptor (GPCR) 2 family.In recent years, GPCRs have been found to interact with many proteins besides G proteins, and such non-G protein interactions are unique to individual receptors and have been shown to play significant roles in signal transduction, receptor regulation, or receptor biogenesis (for reviews, see Refs. 7-9). We have demonstrated that activation of opioid receptors stimulates Na ϩ , H ϩ -exchanger 3 activity via NHERF-1/EBP-50 independent of pertussis toxin-sensitive G proteins (10). In this study, we identified proteins interacting with the human opioid receptor (hKOR) by yeast ...

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“…Thus, GEC1 may have chaperone-like effects for many molecules. GEC1 mRNA has been shown to be up-regulated by estrogen (11,53); therefore, GEC1 may be important in sex differences of some biological functions.…”

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GEC1-κ Opioid Receptor Binding Involves Hydrophobic Interactions

Chen

Kotsikorou

et al. 2009

Journal of Biological Chemistry

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We demonstrated previously that the protein GEC1 (glandular epithelial cell 1) bound to the human opioid receptor (hKOPR) and promoted cell surface expression of the receptor by facilitating its trafficking along the secretory pathway. Modeling studies revealed that the interaction was mediated via direct contacts between the kinked hydrophobic fragment in hKOPR C-tail and the curved hydrophobic surface in GEC1 around the S2 ␤-strand. Intramolecular Leu 44 -Tyr 109 interaction in GEC1 was important, likely by maintaining its structural integrity. Microtubule binding mediated by the GEC1 N-terminal domain was essential for the GEC1 effect. Expression of GEC1 also increased cell surface levels of the GluR1 subunit and the prostaglandin EP3.f receptor, which have FPXXM and FPXM sequences, respectively. With its widespread distribution in the nervous system and its predominantly hydrophobic interactions, GEC1 may have chaperone-like effects for many cell surface proteins along the biosynthesis pathway.

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Identification and characterization of an early estrogen-regulated RNA in cultured guinea-pig endometrial cells

Cited by 35 publications

References 14 publications

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

High expression of gabarapl1 is associated with a better outcome for patients with lymph node-positive breast cancer

GEC1 Interacts with the κ Opioid Receptor and Enhances Expression of the Receptor

GEC1-κ Opioid Receptor Binding Involves Hydrophobic Interactions

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