Functional characterization of multiple domains involved in the subcellular localization of the hematopoietic Pbx interacting protein (HPIP)

Abramovich, Carolina; Chavez, Elizabeth A.; Lansdorp, Peter M.; Humphries, R. Keith

doi:10.1038/sj.onc.1205784

Cited by 33 publications

(22 citation statements)

References 31 publications

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“…The Pbx1/NMHCB interaction also supports the hypothesis that the actin cytoskeleton may play a role in the accurate regulation of the nuclear import of Pbx1. In agreement with this idea, the Haematopoietic Pbx1 Interacting Protein (HPIP), first identified as a PBX partner (Abramovich et al, 2000), has the potential to be a nucleocytoplasmic shuttle protein since it contains a NLS, a NES and a cytoskeletonbinding domain (Abramovich et al, 2002). Thus, the association of HPIP with the cytoskeleton may provide a regulatory mechanism controlling the availability of functional nuclear Pbx proteins.…”

Section: Resultsmentioning

confidence: 74%

PBX proteins: much more than Hox cofactors

Laurent¹,

Bihan²,

Omilli³

et al. 2008

Int. J. Dev. Biol.

101

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Section: Resultsmentioning

confidence: 74%

PBX proteins: much more than Hox cofactors

Laurent¹,

Bihan²,

Omilli³

et al. 2008

Int. J. Dev. Biol.

101

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“…Using the yeast two-hybrid system, we have identified an ER␣-interacting protein called hematopoietic PBX-interacting protein (HPIP; also known as PBX-interacting protein). HPIP is a transcriptional repressor of PBX1 (11) and has been shown to be associated with microtubules through a leucine-rich domain (12). Our data suggest that HPIP mediates binding of ER␣ with tubulins.…”

mentioning

confidence: 60%

“…Because HPIP contains both nuclear localization signals (NLS) and nuclear export signals (NES) (12) and ER␣ interacts with HPIP (this study), signals affecting microtubule-HPIP-ER␣ interaction may also influence HPIP and ER␣ nuclear localization and, hence, modify ER␣ transcriptional activity. In this context, it is notable that estrogen has been shown to inhibit the assembly of microtubules (15).…”

Section: Discussionmentioning

confidence: 99%

An inherent role of microtubule network in the action of nuclear receptor

Manavathi

Acconcia

Rayala

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

110

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Estrogen receptor ␣ (ER␣) functions as both a transcription factor and a mediator of rapid estrogen signaling. Recent studies have shown a role for ER␣-interacting membranous and cytosolic proteins in ER␣ action, but our understanding of the role of the microtubule network in the modulation of ER␣ signaling remains unclear. Here we found that endogenous ER␣ associates with microtubules through the microtubule-binding protein hematopoietic PBX-interaction protein (HPIP). Biochemical and RNA-interference studies demonstrated that HPIP influences ER␣-dependent rapid estrogen signaling by acting as a scaffold protein and recruits Src kinase and the p85 subunit of phosphatidylinositol 3-kinase to a complex with ER␣, which in turn stimulates AKT and MAPK. We also found that ER␣ interacts with ␤-tubulin through HPIP. Destabilization of microtubules activated ER␣ signaling, whereas stabilization of microtubules repressed ER␣ transcriptional activity in a HPIP-dependent manner. These findings revealed a role for HPIPmicrotubule complex in regulating 17␤-estradiol-ER␣ responses in mammalian cells and discovered an inherent role of microtubules in the action of nuclear receptor.17␤-estradiol ͉ estrogen receptor ͉ hematopoietic PBX-interaction protein E strogen regulates a plethora of functionally divergent physiological processes including development, homeostasis, and reproduction (1). The diversity of estrogen action results in part from the ability of estrogen receptors (ERs) to act both as transcription factors that regulate gene expression (i.e., genomic effects) and as signaling proteins that rapidly recruit and activate kinase-dependent signaling pathways (rapid effects). There is growing evidence that a subpopulation of the conventional nuclear steroid receptor localized in the vicinity of the cell membrane mediates many of the rapid signaling actions of steroid hormones; however, membrane receptors unrelated to conventional steroid receptors have also been implicated (2, 3). Several studies support the concept that estrogen can activate multiple cytosolic signaling pathways through direct interactions of conventional estrogen receptor (ER␣ or ER␤) with various cytoplasmic and membranous proteins, including kinases and adaptor proteins, by forming different multiprotein complexes (2, 4). In addition, sequestration of ER by MTA1s (metastasisassociated antigen 1 short form) also triggers estrogen rapid signaling. So it appears that relative subcellular distribution of ERs plays a critical role in estrogen signaling. Besides these mechanistic studies, recent reports have suggested that extranuclear estrogen signaling is directly implicated in cell migration through actin cytoskeleton remodeling (5).Microtubules are structural components of the cytoskeleton required for cell motility that regulate a variety of signaling pathways, including the inducible nitric oxide synthase, NF-B, ERK, JNK, Wnt, and Hedgehog signaling pathways (6). The functional role of microtubules in signal transduction has been further elucidated ...

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“…That study suggested investigating the possible relation of HPIP with signaling pathways (Manavathi et al, 2006). At that point, the only pertinent literature described HPIP as a novel protein detected only in proliferative cells (Manavathi et al, 2006;Abramovich et al, 2000Abramovich et al, , 2002. Our hypothesis was to show the presence of HPIP in neurons and a possible relationship among HPIP-microtubule-estrogen receptors and signaling pathways.…”

Section: Fold Change In Hpipmentioning

confidence: 90%

“…It has been shown that HPIP may be a tether between ER and microtubules. Some studies showed that short-term estrogen treatment increased ER interaction with the HPIP-microtubule complex (Manavathi et al, 2006;Abramovich et al, 2000Abramovich et al, , 2002.…”

Section: Introductionmentioning

confidence: 98%