PELP1-A novel estrogen receptor-interacting protein

Darrell W Brann, Quanguang Zhang, Rui Min Wang, Virendra B. Mahesh, Ratna K. Vadlamudi

Research output: Contribution to journalReview article

33 Citations (Scopus)

Abstract

PELP1 (proline-, glutamic acid-, and leucine-rich protein-1) is a novel estrogen receptor (ER)-interacting protein that has been implicated to be important for mediation of both the genomic and nongenomic signaling of 17β-estradiol (E2). PELP1 contains ten nuclear receptor-interacting boxes (LXXLL motifs), which allow it to interact with ER and other nuclear hormone receptors, a zinc finger, a glutamic acid-rich domain, and two proline-rich domains. The proline-rich regions contain several consensus PXXP motifs, which allow PELP1 to couple the ER with SH3 domain-containing kinase signaling proteins, such as Src and PI3K P85 regulatory subunit. PELP1 is expressed in many different brain regions, including the hippocampus, hypothalamus, and cerebral cortex. Further work has demonstrated that PELP1 is colocalized with ER-α in neurons in various brain regions. PELP1 is primarily expressed in neurons, with some expression also observed in glia. Subcellular localization studies revealed that PELP1 is highly localized in the cell nucleus of neurons, with some cytoplasm localization as well, and PELP1 is also localized at synaptic sites. Work in other tissues has demonstrated that PELP1 is critical for nongenomic and genomic signaling by E2, as PELP1 knockdown studies significantly attenuates E2-induced activation of ERK and Akt signaling pathways, and inhibits E2 genomic transcriptional effects on gene expression in breast cancer cells. Preliminary studies in the brain, suggests that similar roles may exist for PELP1 in the brain, but this remains to be established, and further work to characterize the precise roles and functions of PELP1 in the brain are needed.

Original languageEnglish (US)
Pages (from-to)2-7
Number of pages6
JournalMolecular and Cellular Endocrinology
Volume290
Issue number1-2
DOIs
StatePublished - Aug 13 2008

Fingerprint

Receptor-Interacting Protein Serine-Threonine Kinases
Estrogen Receptors
Brain
Neurons
Cytoplasmic and Nuclear Receptors
Proline
human PELP1 protein
estrophilin
Cells
src Homology Domains
Zinc Fingers
Cell Nucleus
Phosphatidylinositol 3-Kinases
Gene expression
Neuroglia
Cerebral Cortex
Protein Kinases
Hypothalamus
Zinc

Keywords

  • Estradiol
  • Genomic
  • Hippocampus
  • Nongenomic
  • Signaling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

PELP1-A novel estrogen receptor-interacting protein. / Brann, Darrell W; Zhang, Quanguang; Wang, Rui Min; Mahesh, Virendra B.; Vadlamudi, Ratna K.

In: Molecular and Cellular Endocrinology, Vol. 290, No. 1-2, 13.08.2008, p. 2-7.

Research output: Contribution to journalReview article

Brann, Darrell W ; Zhang, Quanguang ; Wang, Rui Min ; Mahesh, Virendra B. ; Vadlamudi, Ratna K. / PELP1-A novel estrogen receptor-interacting protein. In: Molecular and Cellular Endocrinology. 2008 ; Vol. 290, No. 1-2. pp. 2-7.
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