Timeless Is a Novel Estrogen Receptor Co-activator Involved in Multiple Signaling Pathways in MCF-7 Cells
Copyright © 2018. Published by Elsevier Ltd..
Activation of estrogen receptor α (ERα) stimulates cell division and tumor growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homolog of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator. Timeless binds to ERα and enhances its transcriptional activity. Overexpressing Timeless increases PARP1 expression and enhances ERα-induced gene regulation through the proximal LXXLL motif on Timeless protein and ERα PARylation. Finally, Timeless is recruited with ERα on the GREB1 and cMyc promoters. These data, the first to link Timeless to steroid hormone function, provide a mechanistic basis for its clinical association with tamoxifen resistance. Thus, our results identify Timeless as another key regulator of ERα in controlling ERα transactivation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:430 |
|---|---|
| Enthalten in: |
Journal of molecular biology - 430(2018), 10 vom: 11. Mai, Seite 1531-1543 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Magne Nde, Chantal Beatrice [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 13.05.2019 Date Revised 16.08.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jmb.2018.03.008 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM282113398 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM282113398 | ||
| 003 | DE-627 | ||
| 005 | 20231225033159.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jmb.2018.03.008 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0940.xml |
| 035 | |a (DE-627)NLM282113398 | ||
| 035 | |a (NLM)29555554 | ||
| 035 | |a (PII)S0022-2836(18)30136-0 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Magne Nde, Chantal Beatrice |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Timeless Is a Novel Estrogen Receptor Co-activator Involved in Multiple Signaling Pathways in MCF-7 Cells |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.05.2019 | ||
| 500 | |a Date Revised 16.08.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018. Published by Elsevier Ltd. | ||
| 520 | |a Activation of estrogen receptor α (ERα) stimulates cell division and tumor growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homolog of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator. Timeless binds to ERα and enhances its transcriptional activity. Overexpressing Timeless increases PARP1 expression and enhances ERα-induced gene regulation through the proximal LXXLL motif on Timeless protein and ERα PARylation. Finally, Timeless is recruited with ERα on the GREB1 and cMyc promoters. These data, the first to link Timeless to steroid hormone function, provide a mechanistic basis for its clinical association with tamoxifen resistance. Thus, our results identify Timeless as another key regulator of ERα in controlling ERα transactivation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a breast cancer | |
| 650 | 4 | |a coactivator | |
| 650 | 4 | |a estrogen receptor | |
| 650 | 4 | |a tamoxifen | |
| 650 | 7 | |a Cell Cycle Proteins |2 NLM | |
| 650 | 7 | |a ESR1 protein, human |2 NLM | |
| 650 | 7 | |a Estrogen Receptor alpha |2 NLM | |
| 650 | 7 | |a GREB1 protein, human |2 NLM | |
| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a MYC protein, human |2 NLM | |
| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-myc |2 NLM | |
| 650 | 7 | |a TIMELESS protein, human |2 NLM | |
| 650 | 7 | |a PARP1 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.4.2.30 |2 NLM | |
| 650 | 7 | |a Poly (ADP-Ribose) Polymerase-1 |2 NLM | |
| 650 | 7 | |a EC 2.4.2.30 |2 NLM | |
| 700 | 1 | |a Casas Gimeno, Gloria |e verfasserin |4 aut | |
| 700 | 1 | |a Docanto, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Knower, Kevin C |e verfasserin |4 aut | |
| 700 | 1 | |a Young, Morag J |e verfasserin |4 aut | |
| 700 | 1 | |a Buehn, Jakob |e verfasserin |4 aut | |
| 700 | 1 | |a Sayed, Edris |e verfasserin |4 aut | |
| 700 | 1 | |a Clyne, Colin D |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of molecular biology |d 1960 |g 430(2018), 10 vom: 11. Mai, Seite 1531-1543 |w (DE-627)NLM000006777 |x 1089-8638 |7 nnns |
| 773 | 1 | 8 | |g volume:430 |g year:2018 |g number:10 |g day:11 |g month:05 |g pages:1531-1543 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jmb.2018.03.008 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 430 |j 2018 |e 10 |b 11 |c 05 |h 1531-1543 | ||