LMP4 regulates Tbx5 protein subcellular localization and activity

Camarata, Troy; Bimber, Benjamin N.; Kulisz, Andre; Chew, Teng Leong; Yeung, Jennifer; Simon, Hans Georg

doi:10.1083/jcb.200511109

Cited by 37 publications

(79 citation statements)

References 58 publications

(103 reference statements)

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“…Moreover, T was localized to both the chorionic nuclei and cytoplasm. That T-box proteins are not restricted to the nuclei of cells is becoming increasingly well documented (Bimber et al, in press;Camarata et al, 2006), and adds to the further complexity of this family of proteins.…”

Section: Chorio-allantoic (C-a) Union (4-6-s ∼85 Dpc)mentioning

confidence: 99%

The murine allantois: emerging paradigms in development of the mammalian umbilical cord and its relation to the fetus

Inman

Downs

2007

Genesis

102

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Summary: The fertilized egg of the mammal gives rise to the embryo and its extraembryonic structures, all of which develop in intimate relation with each other. Yet, whilst the past several decades have witnessed a vast number of studies on the embryonic component of the conceptus, study of the extraembryonic tissues and their relation to the fetus have been largely ignored. The allantois, precursor tissue of the mature umbilical cord, is a universal feature of all placental mammals that establishes the vital vascular bridge between the fetus and its mother. The allantois differentiates into the umbilical blood vessels, which become secured onto the chorionic component of the placenta at one end and onto the fetus at the other. In this way, fetal blood is channeled through the umbilical cord for exchange with the mother. Despite the importance of this vascular bridge, little is known about how it is made. The aim of this review is to address current understanding of the biology of the allantois in the mouse and genetic control of its features and functions, and to highlight new paradigms concerning the developmental relationship between the fetus and its umbilical cord. genesis 45: 237-258,

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Section: Chorio-allantoic (C-a) Union (4-6-s ∼85 Dpc)mentioning

confidence: 99%

The murine allantois: emerging paradigms in development of the mammalian umbilical cord and its relation to the fetus

Inman

Downs

2007

Genesis

102

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“…For example, Keap1, an actin-binding protein, controls the transactivity of Nrf2 by retaining Nrf2 in the cytoplasm (Itoh et al, 1999). LMP-4, which is associated with the actin cytoskeleton, indirectly regulates the transcription of Tbx5 target genes, Fgf10 and ANF, through trapping Tbx5 in the cytoplasm (Camarata et al, 2006). Therefore, it is possible that Sddr sequesters an essential molecule for ES cell differentiation in the cytoskeleton to prevent expression of differentiation-associated genes.…”

Section: Discussionmentioning

confidence: 99%

A stem cell-derived gene (Sddr) negatively regulates differentiation of embryonic stem cells

Miura¹,

Ueda²,

Takao³

et al. 2010

Int. J. Dev. Biol.

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Embryonic stem (ES) cells, derived from the inner cell mass of blastocysts, are pluripotent and continue to self-renew. To better understand the molecular mechanisms underlying self-renewal, we have been searching for a gene(s) which is specifically expressed in selfrenewing ES cells. Here we report the isolation and characterization of a novel gene, Sddr (stem cell-derived differentiation regulator). Sddr was highly expressed in undifferentiated ES cells, and its expression was downregulated upon differentiation. In addition to ES cells, Sddr expression was observed strongly in ovary, and weakly in lung. Immunostaining and cellular fractionation analyses suggested that Sddr is a cytoplasmic protein associated with the cytoskeleton. Sddr-null ES cells showed no remarkable abnormalities in their undifferentiated state. In contrast, in differentiating Sddr-null cells, induction of several differentiation-associated markers was enhanced, and downregulation of self-renewal marker genes was accelerated, as compared with wild-type cells. These results suggest that although it is dispensable for ES cell self-renewal, Sddr is a negative regulator of ES cell differentiation.

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“…Work with chicken primary epicardial cells revealed that endogenous Tbx5 and LMP4 subcellular localization changes in response to differentiation stimuli (13). While the nature of the signal remains elusive, these in vitro differentiation studies provided the first indications that Tbx5 subcellular localization is not dependent solely on the presence of LMP4 within the cell but, rather, on a regulated event.…”

mentioning

confidence: 88%

“…In transfected cells, coexpression of the cytoplasmic LMP4 induces the relocalization of Tbx5 from the nucleus to the cytoplasm, where the Tbx5-LMP4 complex associates with the actin cytoskeleton (30). In the presence of LMP4, Tbx5 shuttles dynamically between the nucleus and the cytoplasm, thus allowing LMP4 to regulate the nuclear availability of Tbx5 and in turn modulate the transcriptional activity of the protein (13).…”

mentioning

confidence: 99%

An Evolutionarily Conserved Nuclear Export Signal Facilitates Cytoplasmic Localization of the Tbx5 Transcription Factor

Kulisz

Simon

2008

Molecular and Cellular Biology

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During cardiac development, the T-box transcription factor Tbx5 displays dynamic changes in localization from strictly nuclear to both nuclear and cytoplasmic to exclusively cytoplasmic along the actin cytoskeleton in cells coexpressing its binding protein LMP4. Although nuclear localization signals (NLSs) have been described, the mechanism by which Tbx5 exits the nucleus remained elusive. Here, we describe for Tbx5 a nuclear export signal (NES) that is recognized by the CRM1 export protein. Site-directed mutagenesis of a critical amino acid(s) within this sequence determined the functionality of this NES. Confocal localization studies and luciferase transcriptional reporter assays with NES mutant Tbx5 forms demonstrated retention in the nucleus, regardless of the presence of LMP4. Coimmunoprecipitation and pharmacological interference studies demonstrated a direct interaction between Tbx5 and CRM1, revealing that Tbx5 is using the CRM1 pathway for nuclear export. In addition to Tbx5, we identified NESs in all T-box proteins and demonstrated interaction of the family members Tbx3 and Brachyury with the CRM1 exporter, suggesting general significance. This first demonstration of evolutionarily conserved NESs in all T-box proteins in conjunction with NLSs indicates a primordial function of T-box proteins to dynamically shuttle between nuclear and cytoplasmic compartments of the cell.

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LMP4 regulates Tbx5 protein subcellular localization and activity

Cited by 37 publications

References 58 publications

The murine allantois: emerging paradigms in development of the mammalian umbilical cord and its relation to the fetus

The murine allantois: emerging paradigms in development of the mammalian umbilical cord and its relation to the fetus

A stem cell-derived gene (Sddr) negatively regulates differentiation of embryonic stem cells

An Evolutionarily Conserved Nuclear Export Signal Facilitates Cytoplasmic Localization of the Tbx5 Transcription Factor

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