The Tuberous Sclerosis 2 Gene Product Can Localize to Nuclei in a Phosphorylation-Dependent Manner

Lou, Dingyuan; Griffith, Nicole

doi:10.1006/mcbr.2001.0307

Cited by 32 publications

(41 citation statements)

References 31 publications

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“…Our previous studies strongly supported the hypothesis that phosphorylation events play a role in tuberin nuclear localization (15). Furthermore, published (9) and unpublished studies working with tuberin constructs extensively truncated at its amino terminus suggested that the phosphorylation domain involved in this selective activity most likely resides somewhere in the extreme carboxyl terminus of tuberin.…”

Section: Phosphorylation Of Ser 1798 Of the Tuberin Protein Regulatessupporting

confidence: 83%

“…This is supported by subcellular localization studies of tuberin-hamartin complexes in human fetuses and tissues (12), biochemical fractionation studies (13)(14)(15), and functional studies on tuberin and hamartinassociated signaling pathways (15,16). Our previously published data provide evidence for the direct involvement of tuberin in nuclear events and, more specifically, in estrogen genomic signaling; here too, the preponderance of evidence suggests that this activity is in the absence of any hamartin interactions (10,15,17).…”

Section: Introductionmentioning

confidence: 57%

“…In previous work, we showed that tuberin could transiently localize to the nucleus and that this localization was associated with phosphorylation events within the cell (15). In an extension of those studies, we analyzed the general effects of serum starvation on nuclear localization of overexpressed green fluorescent protein (GFP) -tagged tuberin (Fig.…”

Section: Tuberin Can Dynamically Localize To the Nucleusmentioning

confidence: 99%

“…Cells were ultimately fixed with paraformaldehyde and analyzed by fluorescence microscopy at Â60 magnification. serum starved, serum starved followed by a time course stimulation with PMA (15,30,45, and 60 minutes), or treated with vehicle alone (DMSO) as indicated (Fig. 5C, top).…”

Section: Phorbol Esters Stimulate Phosphorylation Of Ser 1798 and Nucmentioning

confidence: 99%

“…TsA201 cells were transfected with either mutant Flag-TSC2 S1798A (rows 1 and 2) or wild-type Flag-TSC2 (rows 3 and 4). Cells were then either maintained in normal serum -containing media or serum starved followed by a time course of PMA treatment (15,30,45, and 60 minutes). Cells were harvested, separated into cytoplasmic and nuclear fractions, and Flag-tagged proteins were isolated from fractions using anti-Flag agarose.…”

Section: Phorbol Esters Stimulate Phosphorylation Of Ser 1798 and Nucmentioning

confidence: 99%

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Tuberin Nuclear Localization Can Be Regulated by Phosphorylation of Its Carboxyl Terminus

York

Lou

2006

Molecular Cancer Research

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Tuberin, the tuberous sclerosis 2 (TSC2) gene product, has been identified as a tumor suppressor protein genetically implicated in the pathology of tuberous sclerosis and the female-specific lung disease lymphangioleiomyomatosis. Tuberin and its predominant cytoplasmic binding partner hamartin have been shown to complex with a variety of intracellular signaling regulators and affect the processes of protein translation, cellular proliferation, cellular migration, and cellular transcription. In previous studies, we have presented evidence for tuberin binding to the calcium-dependent intracellular signaling protein calmodulin (CaM), overlap of tuberin CaM binding domain with a binding domain for estrogen receptor A, and the phosphorylation-associated nuclear localization of tuberin. In the study presented here, we expand our findings on the mechanism of tuberin nuclear localization to show that the CaM-estrogen receptor-A binding domain of tuberin can also serve as a tuberin nuclear localization sequence. Furthermore, we identify an Akt/p90 ribosomal S6 kinase-1 phosphorylation site within the carboxyl terminus of tuberin that can regulate tuberin nuclear localization and significantly affect the ability of tuberin to modulate estrogen genomic signaling events. These findings suggest a link between tuberin nuclear localization and a variety of intracellular signaling events that have direct implications with respect to the role of tuberin in the pathology of tuberous sclerosis and lymphangioleiomyomatosis. (Mol Cancer Res 2006;4(11):885 -97)

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Section: Phosphorylation Of Ser 1798 Of the Tuberin Protein Regulatessupporting

confidence: 83%

Section: Introductionmentioning

confidence: 57%

Section: Tuberin Can Dynamically Localize To the Nucleusmentioning

confidence: 99%

Section: Phorbol Esters Stimulate Phosphorylation Of Ser 1798 and Nucmentioning

confidence: 99%

Section: Phorbol Esters Stimulate Phosphorylation Of Ser 1798 and Nucmentioning

confidence: 99%

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Tuberin Nuclear Localization Can Be Regulated by Phosphorylation of Its Carboxyl Terminus

York

Lou

2006

Molecular Cancer Research

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The non‐canonical nuclear functions of key players of the PI3K‐AKT‐MTOR pathway

Gupta

Kumar

Chaudhuri

et al. 2022

Journal Cellular Physiology

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The PI3K-AKT-MTOR signal transduction pathway is one of the essential signalling cascades within the cell due to its involvement in many vital functions. The pathway initiates with the recruitment of phosphatidylinositol-3 kinases (PI3Ks) onto the plasma membrane, generating 4,4,5) P 3 ] and subsequently activating AKT. Being the central node of the PI3K network, AKT activates the mechanistic target of rapamycin kinase complex 1 (MTORC1) via Tuberous sclerosis complex 2 inhibition in the cytoplasm. Although the cytoplasmic role of the pathway has been widely explored for decades, we now know that most of the effector molecules of the PI3K axis diverge from the canonical route and translocate to other cell organelles including the nucleus. The presence of phosphoinositides (PtdIns) inside the nucleus itself indicates the existence of a nuclear PI3K signalling. The nuclear localization of these signaling components is evident in regulating many nuclear processes like DNA replication, transcription, DNA repair, maintenance of genomic integrity, chromatin architecture, and cell cycle control. Here, our review intends to present a comprehensive overview of the nuclear functions of the PI3K-AKT-MTOR signaling biomolecules.

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A Calmodulin Binding Site in the Tuberous Sclerosis 2 Gene Product Is Essential for Regulation of Transcription Events and Is Altered by Mutations Linked to Tuberous Sclerosis and Lymphangioleiomyomatosis

Noonan

Lou

Griffith

et al. 2002

Archives of Biochemistry and Biophysics

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The Tuberous Sclerosis 2 Gene Product Can Localize to Nuclei in a Phosphorylation-Dependent Manner

Cited by 32 publications

References 31 publications

Tuberin Nuclear Localization Can Be Regulated by Phosphorylation of Its Carboxyl Terminus

Tuberin Nuclear Localization Can Be Regulated by Phosphorylation of Its Carboxyl Terminus

The non‐canonical nuclear functions of key players of the PI3K‐AKT‐MTOR pathway

A Calmodulin Binding Site in the Tuberous Sclerosis 2 Gene Product Is Essential for Regulation of Transcription Events and Is Altered by Mutations Linked to Tuberous Sclerosis and Lymphangioleiomyomatosis

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