What question did this study set out to answer?

To identify the structural domains and receptor interactions of TGF-β type I and type II receptors required to down-regulate cyclin A expression and inhibit cell proliferation.

October 1, 1995Journal of Biological ChemistryOpen Access

Transforming Growth Factor-β (TGF-β)-induced Down-regulation of Cyclin A Expression Requires a Functional TGF-β Receptor Complex

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Authors

XFXin‐Hua FengShaoxing University EFEllen FilvaroffBristol-Myers Squibb (United States)RDRik DerynckBoston University

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Implication

In vitro study reveals that TGF-beta down-regulates cyclin A via a functional heteromeric receptor complex in epithelial cells, indicating shared mechanisms for growth arrest.

Key Points

To identify the structural domains and receptor interactions of TGF-β type I and type II receptors required to down-regulate cyclin A expression and inhibit cell proliferation.
Generated a luciferase reporter assay utilizing a 760-base pair fragment of the human cyclin A promoter to quantify TGF-β-mediated transcriptional repression in Mv1Lu epithelial cells.
Assayed wild-type, chimeric (RI-RII and RII-RI), truncated, and kinase-inactive TGF-β receptors in receptor-deficient cell lines alongside a PAI-1 promoter reporter.
TGF-β-mediated suppression of cyclin A was absent in RI- or RII-deficient cells but was restored by expressing wild-type receptors or co-expressing reciprocal chimeric pairs (RI-RII and RII-RI).
Receptor mutants lacking cytoplasmic domains or kinase activity exerted dominant-negative inhibition over TGF-β-induced cyclin A repression.
The juxtamembrane domain preceding the kinase domain was indispensable for receptor function in both RI and RII, whereas the C-terminal cytoplasmic tail was dispensable.

Cite This Study

Feng et al. (1995) studied this question.

synapsesocial.com/papers/6a727f2a87f92105712896cc https://doi.org/10.1074/jbc.270.41.24237

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Implication

In vitro study reveals that TGF-beta down-regulates cyclin A via a functional heteromeric receptor complex in epithelial cells, indicating shared mechanisms for growth arrest.

Transforming Growth Factor-β (TGF-β)-induced Down-regulation of Cyclin A Expression Requires a Functional TGF-β Receptor Complex

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Implication

Key Points

Cite This Study

Transforming Growth Factor-β (TGF-β)-induced Down-regulation of Cyclin A Expression Requires a Functional TGF-β Receptor Complex

Discussion

Member takes

Implication

Key Points

Cite This Study

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