PELP1: a Key Mediator of Oestrogen Signalling and Actions in the Brain

Overview

Journal J Neuroendocrinol

Specialty Endocrinology

Date 2017 May 10

PMID 28485080

Citations 9

Authors

R Thakkar

G R Sareddy

Q Zhang

R Wang

R K Vadlamudi

D Brann

Affiliations

Soon will be listed here.

Abstract

Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) is an oestrogen receptor (ER) coregulator protein identified by our collaborative group. Work from our laboratory and others has shown that PELP1 is a scaffold protein that interacts with ERs and kinase signalling factors, as well as proteins involved in chromatin remodelling and DNA repair. Its role in mediating 17β-oestradiol (E ) signalling and actions has been studied in detail in cancer cells, although only recently has attention turned to its role in the brain. In this review, we discuss the tissue, cellular and subcellular localisation of PELP1 in the brain. We also discuss recent evidence from PELP1 forebrain-specific knockout mice demonstrating a critical role of PELP1 in mediating both extranuclear and nuclear ER signalling in the brain, as well as E -induced neuroprotection, anti-inflammatory effects and regulation of cognitive function. Finally, the PELP1 interactome and unique gene network regulated by PELP1 in the brain is discussed, especially because it provides new insights into PELP1 biology, protein interactions and mechanisms of action in the brain. As a whole, the findings discussed in the present review indicate that PELP1 functions as a critical ER coregulator in the brain to mediate E signalling and actions.

Citing Articles

Association between dietary branched-chain amino acids and multiple chronic conditions among older adults in Chinese communities.

Song Y, Zhang J, Luo Z, Wu L, Cai Z, Zhong X Nutr Metab (Lond). 2024; 21(1):56.

PMID: 39080679 PMC: 11290232. DOI: 10.1186/s12986-024-00825-9.

clrDV: a differential variability test for RNA-Seq data based on the skew-normal distribution.

Li H, Khang T PeerJ. 2023; 11:e16126.

PMID: 37790621 PMC: 10544356. DOI: 10.7717/peerj.16126.

Cromolyn platform suppresses fibrosis and inflammation, promotes microglial phagocytosis and neurite outgrowth.

Wang Y, Downey M, Choi S, Shoup T, Elmaleh D Sci Rep. 2021; 11(1):22161.

PMID: 34772945 PMC: 8589953. DOI: 10.1038/s41598-021-00465-6.

Altered Expression of , , and Genes Is Associated with Ovarian Cancer Manifestation.

Englert-Golon M, Andrusiewicz M, Zbikowska A, Chmielewska M, Sajdak S, Kotwicka M Int J Mol Sci. 2021; 22(12).

PMID: 34207568 PMC: 8228770. DOI: 10.3390/ijms22126216.

PELP1 promotes glioblastoma progression by enhancing Wnt/β-catenin signaling.

Sareddy G, Pratap U, Viswanadhapalli S, Pitta Venkata P, Nair B, Krishnan S Neurooncol Adv. 2020; 1(1):vdz042.

PMID: 32309805 PMC: 7147719. DOI: 10.1093/noajnl/vdz042.

References

Chakravarty D, Tekmal R, Vadlamudi R . PELP1: A novel therapeutic target for hormonal cancers. IUBMB Life. 2009; 62(3):162-9. PMC: 2997573. DOI: 10.1002/iub.287. View

Ohshiro K, Rayala S, Kondo S, Gaur A, Vadlamudi R, El-Naggar A . Identifying the estrogen receptor coactivator PELP1 in autophagosomes. Cancer Res. 2007; 67(17):8164-71. DOI: 10.1158/0008-5472.CAN-07-0038. View

Tang H, Zhang Q, Yang L, Dong Y, Khan M, Yang F . GPR30 mediates estrogen rapid signaling and neuroprotection. Mol Cell Endocrinol. 2014; 387(1-2):52-8. PMC: 4019970. DOI: 10.1016/j.mce.2014.01.024. View

Mann M, Krishnan S, Vadlamudi R . Emerging significance of estrogen cancer coregulator signaling in breast cancer. Minerva Ginecol. 2012; 64(1):75-88. View

Kefalopoulou Z, Tzelepi V, Zolota V, Grivas P, Christopoulos C, Kalofonos H . Prognostic value of novel biomarkers in astrocytic brain tumors: nuclear receptor co-regulators AIB1, TIF2, and PELP1 are associated with high tumor grade and worse patient prognosis. J Neurooncol. 2011; 106(1):23-31. DOI: 10.1007/s11060-011-0637-y. View

Thakkar R, Wang R, Sareddy G, Wang J, Thiruvaiyaru D, Vadlamudi R . NLRP3 Inflammasome Activation in the Brain after Global Cerebral Ischemia and Regulation by 17-Estradiol. Oxid Med Cell Longev. 2016; 2016:8309031. PMC: 5097821. DOI: 10.1155/2016/8309031. View

Habashy H, Powe D, Rakha E, Ball G, Macmillan R, Green A . The prognostic significance of PELP1 expression in invasive breast cancer with emphasis on the ER-positive luminal-like subtype. Breast Cancer Res Treat. 2009; 120(3):603-12. DOI: 10.1007/s10549-009-0419-9. View

Daniel A, Gaviglio A, Knutson T, Ostrander J, DAssoro A, Ravindranathan P . Progesterone receptor-B enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1- and estrogen receptor-containing transcription complexes. Oncogene. 2014; 34(4):506-15. PMC: 4112172. DOI: 10.1038/onc.2013.579. View

Khan M, Hadman M, De Sevilla L, Mahesh V, Buccafusco J, Hill W . Cloning, distribution, and colocalization of MNAR/PELP1 with glucocorticoid receptors in primate and nonprimate brain. Neuroendocrinology. 2006; 84(5):317-29. DOI: 10.1159/000097746. View

10.

Cortez V, Samayoa C, Zamora A, Martinez L, Tekmal R, Vadlamudi R . PELP1 overexpression in the mouse mammary gland results in the development of hyperplasia and carcinoma. Cancer Res. 2014; 74(24):7395-405. PMC: 4268231. DOI: 10.1158/0008-5472.CAN-14-0993. View

11.

Dubal D, Zhu H, Yu J, Rau S, Shughrue P, Merchenthaler I . Estrogen receptor alpha, not beta, is a critical link in estradiol-mediated protection against brain injury. Proc Natl Acad Sci U S A. 2001; 98(4):1952-7. PMC: 29363. DOI: 10.1073/pnas.98.4.1952. View

12.

Kumar A, Bean L, Rani A, Jackson T, Foster T . Contribution of estrogen receptor subtypes, ERα, ERβ, and GPER1 in rapid estradiol-mediated enhancement of hippocampal synaptic transmission in mice. Hippocampus. 2015; 25(12):1556-66. PMC: 4644731. DOI: 10.1002/hipo.22475. View

13.

Maurer U, Preiss F, Brauns-Schubert P, Schlicher L, Charvet C . GSK-3 - at the crossroads of cell death and survival. J Cell Sci. 2014; 127(Pt 7):1369-78. DOI: 10.1242/jcs.138057. View

14.

Rajhans R, Nair S, Holden A, Kumar R, Tekmal R, Vadlamudi R . Oncogenic potential of the nuclear receptor coregulator proline-, glutamic acid-, leucine-rich protein 1/modulator of the nongenomic actions of the estrogen receptor. Cancer Res. 2007; 67(11):5505-12. PMC: 2774841. DOI: 10.1158/0008-5472.CAN-06-3647. View

15.

Arnold S, Victor M, Beyer C . Estrogen and the regulation of mitochondrial structure and function in the brain. J Steroid Biochem Mol Biol. 2012; 131(1-2):2-9. DOI: 10.1016/j.jsbmb.2012.01.012. View

16.

Chuang D, Wang Z, Chiu C . GSK-3 as a Target for Lithium-Induced Neuroprotection Against Excitotoxicity in Neuronal Cultures and Animal Models of Ischemic Stroke. Front Mol Neurosci. 2011; 4:15. PMC: 3152742. DOI: 10.3389/fnmol.2011.00015. View

17.

Brann D, Dhandapani K, Wakade C, Mahesh V, Khan M . Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids. 2007; 72(5):381-405. PMC: 2048656. DOI: 10.1016/j.steroids.2007.02.003. View

18.

Sawada M, Alkayed N, Goto S, Crain B, Traystman R, Shaivitz A . Estrogen receptor antagonist ICI182,780 exacerbates ischemic injury in female mouse. J Cereb Blood Flow Metab. 2000; 20(1):112-8. DOI: 10.1097/00004647-200001000-00015. View

19.

Clark S, Pollard K, Rainville J, Vasudevan N . Detection of the Phosphorylation of the Estrogen Receptor α as an Outcome of GPR30 Activation. Methods Mol Biol. 2015; 1366:457-470. DOI: 10.1007/978-1-4939-3127-9_36. View

20.

Fox M, Berzuini C, Knapp L . Cumulative estrogen exposure, number of menstrual cycles, and Alzheimer's risk in a cohort of British women. Psychoneuroendocrinology. 2013; 38(12):2973-82. DOI: 10.1016/j.psyneuen.2013.08.005. View