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PMID: 10611245 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A novel PF/PN motif inhibits nuclear localization and DNA binding activity of the ESX1 homeoprotein.

Molecular and cellular biology ·Vol. 20 ·No. 2 ·2000-01-00 ·Pages 661-71

Yan YT, Stein SM, Ding J, Shen MM, Abate-Shen C

Abstract

Despite their significance for mammalian embryogenesis, the molecular mechanisms that regulate placental growth and development have not been well defined. The Esx1 homeobox gene is of particular interest because it is among the few regulatory genes that have specific expression and function in the placenta during murine development. In addition, the ESX1 protein contains several notable features that are not often associated with homeoproteins, including an atypical homeodomain of the paired-like class, a proline-rich region that contains an SH3 binding motif, and a novel repeat region consisting of prolines alternating with phenylalanines or asparagines that we term the PF/PN motif. We have found that the ESX1 protein is expressed in the labyrinth layer of the placenta in vivo, where its subcellular localization is primarily cytoplasmic. Our results suggest that this unexpected subcellular localization is conferred by the PF/PN motif, which inhibits nuclear localization of ESX1 in cell culture, as well as its DNA binding activity in vitro. Finally, we show that the proline-rich region of ESX1 mediates interactions in vitro with the c-abl SH3 domain as well as with certain WW domains. We propose that the PF/PN motif provides a novel mechanism for regulating nuclear entry and that the essential function of ESX1 during placental development is mediated by its ability to couple cytoplasmic signal transduction events with transcriptional regulation in the nucleus.

MeSH Terms
Alternative Splicing/genetics Amino Acid Motifs Amino Acid Sequence Animals Binding Sites Biological Transport Cell Differentiation Cell Line Cell Nucleus/metabolism Cytoplasm/metabolism DNA/antagonists & inhibitors,genetics,metabolism Female Homeodomain Proteins/antagonists & inhibitors,chemistry,genetics,metabolism Male Mice Molecular Sequence Data Placenta/metabolism Placentation Proline/genetics,metabolism Proto-Oncogene Proteins/antagonists & inhibitors,chemistry,genetics,metabolism Proto-Oncogene Proteins c-abl/chemistry,metabolism RNA, Messenger/analysis,genetics Stem Cells/cytology,metabolism Testis/metabolism Transcription Factors/antagonists & inhibitors,chemistry,genetics,metabolism src Homology Domains
Chemicals
Esx1 protein, mouse Homeodomain Proteins Proto-Oncogene Proteins RNA, Messenger Transcription Factors DNA Proline Proto-Oncogene Proteins c-abl
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Yan Y T
Center for Advanced Biotechnology and Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Stein S M
Ding J
Shen M M
Abate-Shen C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.20.2.661-671.2000
Published
2000-01-00
Pages
661-71
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC85162
Subset
IM
Grants
NICHD NIH HHS · HD33362 · United States
NHLBI NIH HHS · HL60212 · United States
External Links
PubMed source DOI: 10.1128/MCB.20.2.661-671.2000 PMC Full Text View journal details
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