ArticleMolecular and cellular biology2007
Regulation of SRC-3 intercompartmental dynamics by estrogen receptor and phosphorylation.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- Hepatocyte TM4SF5-mediated cytosolic NCOA3 stabilization and macropinocytosis support albumin uptake and bioenergetics for hepatocellular carcinoma progression.Experimental & molecular medicine · 2025Article
- Therapeutic Targeting of Nemo-like Kinase in Primary and Acquired Endocrine-resistant Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- A genome-scale CRISPR Cas9 dropout screen identifies synthetically lethal targets in SRC-3 inhibited cancer cells.Communications biology · 2021Article
- Phosphorylation of steroid receptor coactivator-3 (SRC-3) at serine 857 is regulated by the p38Scientific reports · 2020Article
- Inactivation of Cyclic AMP Response Element Transcription Caused by Constitutive p38 Activation Is Mediated by Hyperphosphorylation-Dependent CRTC2 Nucleocytoplasmic Transport.Molecular and cellular biology · 2019Article
- HER2 Signaling Drives DNA Anabolism and Proliferation through SRC-3 Phosphorylation and E2F1-Regulated Genes.Cancer research · 2016Article
- Use of HCA in subproteome-immunization and screening of hybridoma supernatants to define distinct antibody binding patterns.Methods (San Diego, Calif.) · 2016Article
- ERK3 regulates TDP2-mediated DNA damage response and chemoresistance in lung cancer cells.Oncotarget · 2016Article
- Differential Regulation of Progesterone Receptor-Mediated Transcription by CDK2 and DNA-PK.Molecular endocrinology (Baltimore, Md.) · 2016Article
- CAPER is vital for energy and redox homeostasis by integrating glucose-induced mitochondrial functions via ERR-α-Gabpa and stress-induced adaptive responses via NF-κB-cMYC.PLoS genetics · 2015Article
- Coactivators enable glucocorticoid receptor recruitment to fine-tune estrogen receptor transcriptional responses.Nucleic acids research · 2013Article
- New targets for the antitumor activity of gambogic acid in hematologic malignancies.Acta pharmacologica Sinica · 2013Review
- Cytoplasmic localization of alteration/deficiency in activation 3 (ADA3) predicts poor clinical outcome in breast cancer patients.Breast cancer research and treatment · 2013Article
- The role of AIB1 in breast cancer.Oncology letters · 2012Article
- Steroid receptor coactivator 3 regulates autophagy in breast cancer cells through macrophage migration inhibitory factor.Cell research · 2012Article
- Glucocorticoid-dependent phosphorylation of the transcriptional coregulator GRIP1.Molecular and cellular biology · 2012Article
- Development of subtype-selective oestrogen receptor-based therapeutics.Nature reviews. Drug discovery · 2011Review
- Article
- Ligand-dependent degradation of SRC-1 is pivotal for progesterone receptor transcriptional activity.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Distinctive functions of p160 steroid receptor coactivators in proliferation of an estrogen-independent, tamoxifen-resistant breast cancer cell line.Endocrine-related cancer · 2011Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The steroid receptor coactivator 3 gene (SRC-3) (AIB1/ACTR/pCIP/RAC3/TRAM1) is a p160 family transcription coactivator and a known oncogene. Despite its importance, the functional regulation of SRC-3 remains poorly understood within a cellular context. Using a novel combination of live-cell, high-throughput, and fluorescent microscopy, we report SRC-3 to be a nucleocytoplasmic shuttling protein whose intracellular mobility, solubility, and cellular localization are regulated by phosphorylation and estrogen receptor alpha (ERalpha) interactions. We show that both chemical inhibition and small interfering RNA reduction of the mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MEK1/2) pathway induce a cytoplasmic shift in SRC-3 localization, whereas stimulation by epidermal growth factor signaling enhances its nuclear localization by inducing phosphorylation at T24, S857, and S860, known participants in the phosphocode that regulates SRC-3 activity. Accordingly, the cytoplasmic localization of a nonphosphorylatable SRC-3 mutant further supported these results. In the presence of ERalpha, U0126 also dramatically reduces (i) ligand-dependent colocalization of SRC-3 and ERalpha, (ii) the formation of ER-SRC-3 complexes in cell lysates, and (iii) SRC-3 targeting to a visible, ERalpha-occupied and -regulated prolactin promoter array. Taken together, these results indicate that phosphorylation coordinates SRC-3 coactivator function by linking the probabilistic formation of transient nuclear receptor-coactivator complexes with its molecular dynamics and cellular compartmentalization. Technically and conceptually, these findings have a new and broad impact upon evaluating mechanisms of action of gene regulators at a cellular system level.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.