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Donglai Wang, Ning Kon, Gorka Lasso, Le Jiang, Wenchuan Leng, Wei-Guo Zhu, Jun Qin, Barry Honig, Wei Gu
Although lysine acetylation is now recognized as a general protein modification for both histones and non-histone proteins, the mechanisms of acetylation-mediated actions are not completely understood. Acetylation of the C-terminal domain (CTD) of p53 (also known as TP53) was an early example of non-histone protein acetylation and its precise role remains unclear. Lysine acetylation often creates binding sites for bromodomain-containing 'reader' proteins. Here we use a proteomic screen to identify the oncoprotein SET as a major cellular factor whose binding with p53 is dependent on CTD acetylation status...
September 14, 2016: Nature
Ting Yao, Qinfu Wang, Wenyong Zhang, Aihong Bian, Jinping Zhang
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and accounts for ~80% of all kidney cancer cases. However, the pathogenesis of RCC has not yet been fully elucidated. To interpret the pathogenesis of RCC at the molecular level, gene expression data and bio-informatics methods were used to identify RCC associated genes. Gene expression data was downloaded from Gene Expression Omnibus (GEO) database and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in RCC patients compared with controls...
July 2016: Oncology Letters
Izabela Skibinska, Marek Tomaszewski, Miroslaw Andrusiewicz, Paulina Urbaniak, Roza Czarnecka-Klos, Milud Shadi, Tomasz Kotwicki, Malgorzata Kotwicka
PURPOSE: The aim of this study was to detect and assess the estrogen receptor (ESR) coactivator PELP1 expression within human paraspinal skeletal muscles in patients suffering from idiopathic scoliosis. METHODS: During surgical correction of scoliosis the muscle biopsies harvested in 29 females. Presence of PELP1, ESR1 and ESR2 genes transcripts was studied using RT-qPCR technique while immunohistochemistry and western blot methods were used to detect the PEPL1 protein presence...
2016: PloS One
Gangadhara Reddy Sareddy, Ratna K Vadlamudi
Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein that functions as a coregulator of several transcription factors and nuclear receptors. Notably, the PELP1 protein has a histone-binding domain, recognizes histone modifications and interacts with several chromatin-modifying complexes. PELP1 serves as a substrate of multitude of kinases, and phosphorylation regulates its functions in various complexes. Further, PELP1 plays essential roles in several pathways including hormonal signaling, cell cycle progression, ribosomal biogenesis, and the DNA damage response...
July 1, 2016: Gene
Gangadhara R Sareddy, Quanguang Zhang, Ruimin Wang, Erin Scott, Yi Zou, Jason C O'Connor, Yidong Chen, Yan Dong, Ratna K Vadlamudi, Darrell Brann
17-β estradiol (E2) has been implicated as neuroprotective in a variety of neurodegenerative disorders. However, the underlying mechanism remains unknown. Here, we provide genetic evidence, using forebrain-specific knockout (FBKO) mice, that proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), an estrogen receptor coregulator protein, is essential for the extranuclear signaling and neuroprotective actions of E2 in the hippocampal CA1 region after global cerebral ischemia (GCI). E2-mediated extranuclear signaling (including activation of extracellular signal-regulated kinase and Akt) and antiapoptotic effects [such as attenuation of JNK signaling and increase in phosphorylation of glycogen synthase kinase-3β (GSK3β)] after GCI were compromised in PELP1 FBKO mice...
December 1, 2015: Proceedings of the National Academy of Sciences of the United States of America
Yanzhi Zhang, Jiali Dai, Keely M McNamara, Bing Bai, Mumu Shi, Monica S M Chan, Ming Liu, Hironobu Sasano, Xiuli Wang, Xiaolei Li, Lijuan Liu, Ying Ma, Shuwen Cao, Yanchun Xing, Baoshan Zhao, Yinli Song, Lin Wang
BACKGROUND: Triple-negative breast cancer (TNBC) is associated with an aggressive clinical course due to the lack of therapeutic targets. Therefore, identifying reliable prognostic biomarkers and novel therapeutic targets for patients with TNBC is required. Proline, glutamic acid, leucine rich protein 1 (PELP1) is a novel steroidal receptor co-regulator, functioning as an oncogene and its expression is maintained in estrogen receptor (ER) negative breast cancers. PELP1 has been proposed as a prognostic biomarker in hormone-related cancers, including luminal-type breast cancers, but its significance in TNBC has not been studied...
2015: BMC Cancer
Marianne Hauglid Flågeng, Stian Knappskog, Jennifer Gjerde, Per Eystein Lønning, Gunnar Mellgren
The Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) is an estrogen receptor (ER) coactivator and a proto-oncogene known to be deregulated in endocrine cancers. In breast cancer, PELP1 overexpression has been associated with endocrine therapy resistance. Although PELP1 is known to be regulated by estrogens in vitro, its association with estrogen levels within the tissue of breast cancer patients has not previously been assessed. Here, we determined PELP1 mRNA expression levels in paired samples of normal and malignant breast tissue obtained from 32 postmenopausal and 11 premenopausal women...
2015: PloS One
Bartosz Kazimierz Słowikowski, Bartłomiej Gałęcki, Wojciech Dyszkiewicz, Paweł Piotr Jagodziński
It has been demonstrated that estrogens are able to enhance lung tumorigenesis by estrogen receptor (ER) pathway. ER signaling is a highly complex process that requires a number of different coactivators, including proline-, glutamic acid- and leucine-rich protein-1 (PELP1). We studied PELP1 transcript and protein levels in cancerous and histopathologically unchanged lung tissues obtained from 73 patients diagnosed with non-small cell lung cancer (NSCLC). We observed increased levels of PELP1 transcript (P=0...
July 2015: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Preethi Ravindranathan, Carol A Lange, Ganesh V Raj
No abstract text is available yet for this article.
September 2015: Molecular Endocrinology
Brian J Girard, Tarah M Regan Anderson, Siya Lem Welch, Julie Nicely, Victoria L Seewaldt, Julie H Ostrander
Tamoxifen (Tam) is the only FDA-approved chemoprevention agent for pre-menopausal women at high risk for developing breast cancer. While Tam reduces a woman's risk of developing estrogen receptor positive (ER+) breast cancer, the molecular mechanisms associated with risk reduction are poorly understood. Prior studies have shown that cytoplasmic proline, glutamic acid and leucine rich protein 1 (PELP1) promotes Tam resistance in breast cancer cell lines. Herein, we tested for PELP1 localization in breast epithelial cells from women at high risk for developing breast cancer and found that PELP1 was localized to the cytoplasm in 36% of samples...
2015: PloS One
Samaya R Krishnan, Binoj C Nair, Gangadhara R Sareddy, Sudipa Saha Roy, Mohan Natarajan, Takayoshi Suzuki, Yan Peng, Ganesh Raj, Ratna K Vadlamudi
Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype, occurs in younger women and is associated with poor prognosis. Gain-of-function mutations in TP53 are a frequent occurrence in TNBC and have been demonstrated to repress apoptosis and up-regulate cell cycle progression. Even though TNBC responds to initial chemotherapy, resistance to chemotherapy develops and is a major clinical problem. Tumor recurrence eventually occurs and most patients die from their disease. An urgent need exists to identify molecular-targeted therapies that can enhance chemotherapy response...
April 2015: Breast Cancer Research and Treatment
Valerie Cortez, Cathy Samayoa, Andrea Zamora, Lizatte Martinez, Rajeshwar R Tekmal, Ratna K Vadlamudi
Estrogen receptor (ER) coregulator overexpression promotes carcinogenesis and/or progression of endocrine related-cancers in which steroid hormones are powerful mitogenic agents. Recent studies in our laboratory, as well as others, demonstrated that the estrogen receptor coregulator PELP1 is a proto-oncogene. PELP1 interactions with histone demethylase KDM1 play a critical role in its oncogenic functions and PELP1 is a prognostic indicator of decreased survival in patients with breast cancer. However, the in vivo significance of PELP1 deregulation during initiation and progression of breast cancer remains unknown...
December 15, 2014: Cancer Research
Fernando Chico-Ponce de León, Luis F Gordillo-Domínguez, Vicente González-Carranza, Samuel Torres-García, Constanza García-Delgado, Adriana Sánchez-Boiso, Francisco Arenas-Huertero, Mario Perezpeña-Diazconti, Pilar Eguía-Aguilar, César Baqueiro-Hernández, Guillermo Buenrostro-Márquez, Sonia Martínez-Rodríguez, Patrick Dhellemmes, Eduardo Castro-Sierra
PURPOSE: A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City. METHODS AND RESULTS: Presumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal...
January 2015: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
Zhifeng Ning, Youzhi Zhang, Hanwei Chen, Jiliang Wu, Tieshan Song, Qian Wu, Fuxing Liu
Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a coregulator of estrogen receptors alpha and beta, is a potential protooncogene implicated in several human cancers, including sexual hormone-responsive or sexual hormone-nonresponsive cancers. However, the functions of PELP1 in colorectal cancer remain unclear. In this study, western blot and bioinformatics revealed that PELP1 expression was higher in several colorectal cancer cell lines than in immortalized normal colorectal epithelium. PELP1 silencing by short hairpin RNA promoted the senescence and inhibited the proliferation, colony formation, migration, invasion, and xenograft tumor formation of the CRC cell line HT-29...
2014: Oxidative Medicine and Cellular Longevity
Vijay K Gonugunta, Lu Miao, Gangadhara R Sareddy, Preethi Ravindranathan, Ratna Vadlamudi, Ganesh V Raj
Proline, glutamic acid- and leucine-rich protein 1 (PELP1) is a multi-domain scaffold protein that serves as a platform for various protein-protein interactions between steroid receptors (SRs) and signaling factors and cell cycle, transcriptional, cytoskeletal, and epigenetic remodelers. PELP1 is known to be a coregulator of transcription and participates in the nuclear and extranuclear functions of SRs, ribosome biogenesis, and cell cycle progression. The expression and localization of PELP1 are dysregulated in hormonal cancers including breast and prostate cancers...
August 2014: Endocrine-related Cancer
Wen Xu
Asthma is characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, and coughing. It is usually caused by a combination of complex and incompletely understood environmental and genetic interactions. We obtained gene expression data with high-throughput screening and identified biomarkers of children's asthma using bioinformatics tools. Next, we explained the pathogenesis of children's asthma from the perspective of gene regulatory networks: DAVID was applied to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enriching analysis for the top 3000 pairs of relationships in differentially regulatory network...
2014: International Journal of Genomics
B C Nair, S R Krishnan, G R Sareddy, M Mann, B Xu, M Natarajan, P Hasty, D Brann, R R Tekmal, R K Vadlamudi
Proline-, glutamic acid- and leucine-rich protein-1 (PELP1) is a scaffolding oncogenic protein that functions as a coregulator for a number of nuclear receptors. p53 is an important transcription factor and tumor suppressor that has a critical role in DNA damage response (DDR) including cell cycle arrest, repair or apoptosis. In this study, we found an unexpected role for PELP1 in modulating p53-mediated DDR. PELP1 is phosphorylated at Serine1033 by various DDR kinases like ataxia-telangiectasia mutated, ataxia telangiectasia and Rad3-related or DNAPKc and this phosphorylation of PELP1 is important for p53 coactivation functions...
September 2014: Cell Death and Differentiation
Kristine M Hussey, Hongshan Chen, Christine Yang, Eugene Park, Nasun Hah, Hediye Erdjument-Bromage, Paul Tempst, Matthew J Gamble, W Lee Kraus
MacroH2A1 is a histone variant harboring an ∼25-kDa carboxyl-terminal macrodomain. Due to its enrichment on the inactive X chromosome, macroH2A1 was thought to play a role in transcriptional repression. However, recent studies have shown that macroH2A1 occupies autosomal chromatin and regulates genes in a context-specific manner. The macrodomain may play a role in the modulation of gene expression outcomes via physical interactions with effector proteins, which may depend on the ability of the macrodomain to bind NAD(+) metabolite ligands...
July 2014: Molecular and Cellular Biology
Vijay K Gonugunta, Gangadhara R Sareddy, Samaya Rajeshwari Krishnan, Valerie Cortez, Sudipa Saha Roy, Rajeshwar Rao Tekmal, Ratna K Vadlamudi
Proline, Glutamic acid-, and Leucine-rich Protein 1 (PELP1) is a proto-oncogene that modulates estrogen receptor (ER) signaling. PELP1 expression is upregulated in breast cancer, contributes to therapy resistance, and is a prognostic marker of poor survival. In a subset of breast tumors, PELP1 is predominantly localized in the cytoplasm and PELP1 participates in extranuclear signaling by facilitating ER interactions with Src and phosphoinositide 3-kinase (PI3K). However, the mechanism by which PELP1 extranuclear actions contributes to cancer progression and therapy resistance remains unclear...
June 2014: Molecular Cancer Therapeutics
Yanzhi Zhang, Peng Wang, Mumu Shi, Hironobu Sasano, Monica S M Chan, Jiali Dai, Lunshu Guo, Ming Liu, Xiaoyan Wang, Ying Ma, Lin Wang
BACKGROUND: Disparities of biomarkers' expression in breast cancer across different races and ethnicities have been well documented. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel ER coregulator, has been considered as a promising biomarker of breast cancer prognosis; however, the pattern of PELP1 expression in Chinese women with breast cancer has never been investigated. This study aims to provide useful reference on possible racial or ethnic differences of PELP1 expression in breast cancer by exploring the pattern of PELP1 expression in Chinese women with primary breast cancer...
January 2014: International Journal of Biological Markers
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