Transforming Growth Factor β1 Inhibition of p34<i><sup>cdc2</sup></i> Phosphorylation and Histone H1 Kinase Activity Is Associated with G1/S-Phase Growth Arrest

Howe, Philip H.; Draetta, Giulio; Leof, Edward B.

doi:10.1128/mcb.11.3.1185-1194.1991

Cited by 7 publications

(3 citation statements)

References 32 publications

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“…Unlike other growth factors such as EGF, PDGF, and NGF, whose responses are very rapid, TGFβ is a relatively slower acting growth factor. TGFβ inhibits cell proliferation in late G1 phase of the cell cycle, and its effects on various cell cycle associated cyclin proteins are not seen until 16 h posttreatment (Howe et al, 1991;Reddy et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

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Transforming Growth Factor β (TGFβ)-Induced Nuclear Localization of Apolipoprotein J/Clusterin in Epithelial Cells

et al. 1996

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Apolipoprotein J (apoJ)/clusterin was first identified as an 80 kDa secretory glycoprotein present in most body fluids. It has been implicated in a variety of physiological processes including cellular differentiation and apoptosis. We demonstrate here that in addition to the well characterized secreted form of the protein, there exists an intracellular, nuclear form of apoJ. This intracellular form of the protein is induced to accumulate in the nucleus of two epithelial cell lines (HepG2 and CCL64) in response to treatment with transforming growth factor beta (TGF beta). We demonstrate in vitro that apoJ protein can be translated from two in-frame ATG sites. Initiation from the first ATG encodes for the secretory form of apoJ and initiation from the second ATG, located 33 amino acids downstream of the first and lacking the hydrophobic signal sequence, encodes for a truncated apoJ protein. This shorter form of apoJ is not recognized by microsomes and therefore not glycosylated, and we postulate that it is retained intracellularly and targeted to the nucleus due to the presence of an SV40-like nuclear localization sequence (NLS). This mechanism of nuclear targeting of apoJ occurs in cells since the protein isolated from nuclei of TGF beta-treated cells and the in vitro-translated truncated form are identical by V8 protease analysis. These results suggest that the diverse physiological responses attributed to apoJ may be elicited through a common molecular mechanism involving a previously uncharacterized intracellular form of the protein.

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Section: Resultsmentioning

confidence: 99%

“…The mink lung epithelial cell line, CCL64, is highly sensitive to TGFβ and is routinely used to study TGFβinduced cellular responses (Howe et al, 1991;Reddy et al, 1994). It was of interest, therefore, to determine the effects of TGFβ on both apoJ mRNA and its protein in this cell line.…”

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confidence: 99%

Transforming Growth Factor β (TGFβ)-Induced Nuclear Localization of Apolipoprotein J/Clusterin in Epithelial Cells

et al. 1996

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“…Recently, it has been demonstrated that the RI receptor, in a genetic screening analysis using the two-hybrid system, interacts with the rapamycin binding protein FKBP-12 (Wang et al, 1994). The physiological significance of such binding is unclear; however, the fact that both TGFβ (Howe et al, 1991) and rapamycin (Morice et al, 1993) rapamycin share common signaling components. We also utilized the two-hybrid system (Fields & Song, 1989) to identify receptor-associated proteins but, instead of the RI TGFβ receptor, performed our genetic screen with the cytoplasmic domain of the RII receptor.…”

Section: Resultsmentioning

confidence: 99%

Interaction of Transforming Growth Factor β Receptors with Apolipoprotein J/Clusterin

et al. 1996

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Proteins mediating the transmission of the signal from an activated transforming growth factor beta (TGF beta) receptor complex have not been identified. Using a yeast interaction screen to search for proteins that associate with the type II TGF beta receptor (RII), we isolated a protein which was identical to apolipoprotein J (apoJ)/clusterin. ApoJ interacts with both the type I (RI) and type II (RII) TGF beta receptors but does not interact with the epidermal growth factor (EGF) receptor. The interaction between RII and apoJ occurs through the C-terminal 127 amino acids of RII. Deletion of this region, which contains the kinase insert 2 domain, abrogates binding to apoJ. The binding of apoJ to either the RI and the RII receptors is direct, not requiring other proteins, and is not specific for the alpha or beta subunit of apoJ since both subunits are effective in competing for binding. RI and RII fusion proteins are capable of precipitating the 60 kDa intracellular form of apoJ from [35S]methionine-labeled cellular lysates, suggesting that this form of the protein may play some role in TGF beta signaling or TGF beta receptor processing.

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Spatial control of cell fate using synthetic surfaces to potentiate TGF-β signaling

Li¹,

Klim²,

Derda³

et al. 2011

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

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In organisms, cell-fate decisions result from external cues presented by the extracellular microenvironment or the niche. In principle, synthetic niches can be engineered to give rise to patterned cell signaling, an advance that would transform the fields of tissue engineering and regenerative medicine. Biomaterials that display adhesive motifs are critical steps in this direction, but promoting localized signaling remains a major obstacle. We sought to exert precise spatial control over activation of TGF-β signaling. TGF-β signaling, which plays fundamental roles in development, tissue homeostasis, and cancer, is initiated by receptor oligomerization. We therefore hypothesized that preorganizing the transmembrane receptors would potentiate local TGF-β signaling. To generate surfaces that would nucleate the signaling complex, we employed defined self-assembled monolayers that present peptide ligands to TGF-β receptors. These displays of nondiffusible ligands do not compete with the growth factor but rather sensitize bound cells to subpicomolar concentrations of endogenous TGF-β. Cells adhering to the surfaces undergo TGF-β-mediated growth arrest and the epithelial to mesenchymal transition. Gene expression profiles reveal that the surfaces selectively regulate TGF-β responsive genes. This strategy provides access to tailored surfaces that can deliver signals with spatial control.

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Transforming Growth Factor β1 Inhibition of p34^cdc2 Phosphorylation and Histone H1 Kinase Activity Is Associated with G1/S-Phase Growth Arrest

Cited by 7 publications

References 32 publications

Transforming Growth Factor β (TGFβ)-Induced Nuclear Localization of Apolipoprotein J/Clusterin in Epithelial Cells

Transforming Growth Factor β (TGFβ)-Induced Nuclear Localization of Apolipoprotein J/Clusterin in Epithelial Cells

Interaction of Transforming Growth Factor β Receptors with Apolipoprotein J/Clusterin

Spatial control of cell fate using synthetic surfaces to potentiate TGF-β signaling

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Transforming Growth Factor β1 Inhibition of p34cdc2 Phosphorylation and Histone H1 Kinase Activity Is Associated with G1/S-Phase Growth Arrest

Cited by 7 publications

References 32 publications

Transforming Growth Factor β (TGFβ)-Induced Nuclear Localization of Apolipoprotein J/Clusterin in Epithelial Cells

Transforming Growth Factor β (TGFβ)-Induced Nuclear Localization of Apolipoprotein J/Clusterin in Epithelial Cells

Interaction of Transforming Growth Factor β Receptors with Apolipoprotein J/Clusterin

Spatial control of cell fate using synthetic surfaces to potentiate TGF-β signaling

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Product

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Transforming Growth Factor β1 Inhibition of p34^cdc2 Phosphorylation and Histone H1 Kinase Activity Is Associated with G1/S-Phase Growth Arrest