A5044377323- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- Computational Drug Discovery Methods
- bioluminescence and chemiluminescence research
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Melanoma and MAPK Pathways
- Receptor Mechanisms and Signaling
- Cancer-related Molecular Pathways
- Reproductive System and Pregnancy
- RNA and protein synthesis mechanisms
- Retinoids in leukemia and cellular processes
- Protein Kinase Regulation and GTPase Signaling
- Plant Genetic and Mutation Studies
- Insect Resistance and Genetics
- PI3K/AKT/mTOR signaling in cancer
- MicroRNA in disease regulation
- DNA and Nucleic Acid Chemistry
- Neuroblastoma Research and Treatments
- Click Chemistry and Applications
- Marine Biology and Environmental Chemistry
- Endometriosis Research and Treatment
Baylor College of Medicine
2015-2024
Children's Cancer Center
2020-2021
King Faisal Specialist Hospital & Research Centre
2020
Dan L Duncan Comprehensive Cancer Center
2020
Romanian Academy
2020
University of Chicago
2020
The University of Texas MD Anderson Cancer Center
2020
Southwest Medical University
2018
Zhengzhou University
2018
Guardant (United States)
2018
Cell signaling affects gene expression by regulating the activity of transcription factors. Here, we report that mitogen-activated protein kinase (MAPK) phosphorylation Ets-1 and Ets-2, at a conserved site N terminal to their Pointed (PNT) domains, resulted in enhanced transactivation preferential recruitment coactivators CREB binding (CBP) p300. We discovered this phosphorylation-augmented interaction an unbiased affinity chromatography screen HeLa nuclear extracts using either mock-treated...
In contrast to the well-studied classic MAPKs, such as ERK1/2, little is known concerning regulation and substrates of atypical MAPK ERK3 signaling cascade its function in cancer progression. Here, we report that interacted with phosphorylated steroid receptor coactivator 3 (SRC-3), an oncogenic protein overexpressed multiple human cancers at serine 857 (S857). This ERK3-mediated phosphorylation S857 was essential for interaction SRC-3 ETS transcription factor PEA3, which promotes...
The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) target specific mRNA species for regulation. There is increasing evidence important functional interactions between the miRNA nuclear receptor (NR) signaling networks, with recent data showing estrogen, acting through estrogen receptor, can modulate initial...
Mining of integrated public transcriptomic and ChIP-Seq (cistromic) datasets can illuminate functions mammalian cellular signaling pathways not yet explored in the research literature. Here, we designed a web knowledgebase, Signaling Pathways Project (SPP), which incorporates community classifications pathway nodes (receptors, enzymes, transcription factors co-nodes) their cognate bioactive small molecules. We then mapped over 10,000 or cistromic experiments to node biosample study. To...
We report that neurofibromin, a tumor suppressor and Ras-GAP (GTPase-activating protein), is also an estrogen receptor-α (ER) transcriptional co-repressor through leucine/isoleucine-rich motifs are functionally independent of GAP activity. activity, in turn, does not affect ER binding. Consequently, neurofibromin depletion causes estradiol hypersensitivity tamoxifen agonism, explaining the poor prognosis associated with loss endocrine therapy-treated ER+ breast cancer....
Abstract Cellular responses to the steroid hormones, estrogen (E2), and progesterone (P4) are governed by their cognate receptor’s transcriptional output. However, feed-forward mechanisms that shape cell-type-specific fulcrums for receptors unidentified. Herein, we found a common mechanism between GREB1 regulates differential effect of on hormones in physiological or pathological context. In (receptive) endometrium, controls P4-responses uterine stroma, affecting endometrial receptivity...
Tissue and organ development is a time of exquisite sensitivity to environmental exposures, which can reprogram developing tissues increase susceptibility adult diseases, including cancer. In the prostate, even brief exposure endocrine-disrupting chemicals (EDCs) risk for cancer in adulthood, with disruption epigenome thought play key role this developmental reprogramming. We find that EDC-induced nongenomic phosphoinositide 3-kinase; (PI3K) signaling engages histone methyltransferase...
Abstract Our early-life environment has a profound influence on developing organs that impacts metabolic function and determines disease susceptibility across the life-course. Using rat model for exposure to an endocrine disrupting chemical (EDC), we show causes dysfunction in adulthood reprograms histone marks liver accelerate acquisition of adult epigenomic signature. This reprogramming persists long after initial exposure, but many reprogrammed genes remain transcriptionally silent with...
The human steroid receptor RNA activator (SRA) gene encodes both noncoding RNAs (ncRNAs) and protein-generating isoforms. In reporter assays, SRA ncRNA enhances nuclear myogenic differentiation 1 (MyoD)-mediated transcription but also participates in specific corepressor complexes, serving as a distinct scaffold. That levels might affect some biological functions, such proliferation, apoptosis, steroidogenesis, myogenesis, has been reported. However, the breadth of endogenous target genes...
Approximately 75% of breast cancers are estrogen receptor alpha (ERα)-positive and treatable with endocrine therapies, but often patients develop lethal resistant disease. Frequent mutations (10-40%) in the ligand-binding domain (LBD) codons gene encoding ERα (ESR1) have been identified, resulting ligand-independent, constitutively active receptors. In addition, ESR1 chromosomal translocations can occur, fusion proteins that lack LBD entirely unresponsive to all treatments. Thus, identifying...
The coactivator-associated arginine methyltransferase (CARM1) functions as a regulator of transcription by methylating diverse array substrates. To broaden our understanding CARM1's mechanistic actions, we sought to identify additional substrates for this enzyme. do this, generated CARM1 substrate motif antibodies, and used immunoprecipitation coupled with mass spectrometry cellular targets CARM1, including mediator complex subunit 12 (MED12) the lysine KMT2D. Both these proteins are...
Abstract Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients 22 ER+ cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth...
A subset of environmental chemicals acts as "obesogens" they increase adipose mass and lipid content in livers treated rodents. One the most studied class obesogens are tin-containing that have a central moiety tributyltin (TBT), which bind activate two nuclear hormone receptors, Peroxisome Proliferator Activated Receptor Gamma (PPARG) Retinoid X Alpha (RXRA), at nanomolar concentrations. Here, we tested whether TBT chloride such concentrations may affect neutral level cell line models human...
The conjugated estrogen<b>/</b>bazedoxifene tissue-selective estrogen complex (TSEC) is designed to minimize the undesirable effects of in uterus and breast tissues allow beneficial other estrogen-target tissues, such as bone brain. However, molecular mechanism underlying endometrial safety during TSEC use not fully understood. Estrogen receptor <i>α</i> (ER<i>α</i>)–estrogen response element (ERE)–DNA pull-down assays using HeLa nuclear extracts followed by mass spectrometry–immunoblotting...