Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor

Saporita, Anthony J.; Zhang, Qiuheng; Navai, Neema; Dincer, Zehra; Hahn, Junghyun; Cai, Xiaoyan; Wang, Zhou

doi:10.1016/s1569-9056(03)90641-5

Cited by 33 publications

(58 citation statements)

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“…An LMB-insensitive NES is identified in the LBD of AR (Saporita et al 2003). The AR-NES was shown to be active in the absence of androgen and repressed upon ligand-binding to AR.…”

Section: Discussionmentioning

confidence: 97%

“…The AR-NES was shown to be active in the absence of androgen and repressed upon ligand-binding to AR. ER and mineralocorticoid receptor also harbor a similar functional NES in their LBD (Saporita et al 2003;Kumar et al 2006), suggesting that this ligand-regulatory type of NES is conserved between the steroid receptors. We also found an NES in the LBD of PPARs.…”

Section: Discussionmentioning

confidence: 98%

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Ligand‐dependent nucleo‐cytoplasmic shuttling of peroxisome proliferator‐activated receptors, PPARα and PPARγ

Umemoto

Fujiki

2012

Genes to Cells

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Peroxisome proliferator-activated receptors (PPARs) play important roles in diverse biological processes including metabolisms of sugars and lipids and differentiation of cells such as adipocytes. PPARs are transcription factors belonging to the ligand-dependent hormone receptor group. To function as transcription factors, PPARs translocate into nucleus where they associate with transcription apparatus. However, mechanisms underlying nuclear transport of PPARs remain enigmatic. We show here that PPARa and PPARc dynamically shuttle between nucleus and cytoplasm, although they constitutively and predominantly appear in nucleus. With a series of truncation mutants, we identify that PPAR nuclear transport is mediated by at least two nuclear localization signals (NLSs) in DNA-binding domain (DBD)-hinge and activation function 1 (AF1) regions and their respective receptors including importina/b, importin 7, and an unidentified receptor. PPARs also harbor two nuclear export signals in DBD and ligand-binding domain regions that are recognized by distinct export receptors, calreticulin and CRM1. Moreover, we show that nuclear-cytoplasmic shuttling of PPARs is regulated by respective PPAR ligands and Ca 2+ concentration. Taken together, we suggest that the multiple pathways for the nuclear-cytoplasmic transport of PPARs regulate the biological functions of PPARs in response to external signals.

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“…An LMB-insensitive NES is identified in the LBD of AR (Saporita et al 2003). The AR-NES was shown to be active in the absence of androgen and repressed upon ligand-binding to AR.…”

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

Ligand‐dependent nucleo‐cytoplasmic shuttling of peroxisome proliferator‐activated receptors, PPARα and PPARγ

Umemoto

Fujiki

2012

Genes to Cells

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“…androgen), the NES is masked and unable to be recognized by EXP1. Relocalization of androgen receptor to the cytoplasm can thus only occur when ligand dissociates from the androgen receptor NES (27).…”

Section: Intermolecular Masking Of Nls/nesmentioning

confidence: 99%

Regulation of Nuclear Transport: Central Role in Development and Transformation?

Poon

Jans

2005

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Transport of macromolecules into and out of the nucleus is generally effected by targeting signals that are recognized by specific members of the importin/exportin transport receptor family. The latter mediate passage through the nuclear envelope-embedded nuclear pore complexes (NPCs) by conferring interaction with NPC constituents, as well as with other components of the nuclear transport machinery, including the guanine nucleotide-binding protein Ran. Importantly, nuclear transport is regulated at multiple levels via a diverse range of mechanisms, such as the modulation of the accessibility and affinity of target signal recognition by importins/exportins, with phosphorylation/dephosphorylation as a major mechanism. Alteration of the level of the expression of components of the nuclear transport machinery also appears to be a key determinant of transport efficiency, having central importance in development, differentiation and transformation.

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“…Steroid receptors, including AR, contain two nuclear localization signals, NL1 in the DNA-binding domain and hinge region, and NL2 in the ligand-binding domain (LBD) [4,5]. Recently, we have reported the existence of a nuclear export signal (NES) in the LBD of AR, that causes cytoplasmic localization of the receptor in the absence of ligand [6]. Upon binding hormone, the NES is repressed and AR translocates into the nucleus.…”

Section: Introductionmentioning

confidence: 99%

The Hsp90 inhibitor, 17‐AAG, prevents the ligand‐independent nuclear localization of androgen receptor in refractory prostate cancer cells

Saporita

Wang

2007

The Prostate

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BACKGROUND-Androgen receptor (AR) is the key molecule in androgen-refractory prostate cancer. Despite androgen ablative conditions, AR remains active and is necessary for the growth of androgen-refractory prostate cancer cells. Nuclear localization of AR is a prerequisite for its transcriptional activation. We examined AR localization in androgen-dependent and androgenrefractory prostate cancer cells.

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Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor

Cited by 33 publications

References 0 publications

Ligand‐dependent nucleo‐cytoplasmic shuttling of peroxisome proliferator‐activated receptors, PPARα and PPARγ

Ligand‐dependent nucleo‐cytoplasmic shuttling of peroxisome proliferator‐activated receptors, PPARα and PPARγ

Regulation of Nuclear Transport: Central Role in Development and Transformation?

The Hsp90 inhibitor, 17‐AAG, prevents the ligand‐independent nuclear localization of androgen receptor in refractory prostate cancer cells

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