Convergence of p53 and Transforming Growth Factor β (TGFβ) Signaling on Activating Expression of the Tumor Suppressor Gene maspin in Mammary Epithelial Cells

Wang, Shizhen Emily; Narasanna, Archana; Whitell, Corbin W.; Wu, Frederick Y.; Friedman, David; Arteaga, Carlos L.

doi:10.1074/jbc.m608499200

Cited by 35 publications

(37 citation statements)

References 38 publications

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“…Interestingly, IKK-controlled Maspin repression seems to be NFB-independent in this model (Luo et al, 2007). Although the Maspin promoter is bound by SMADs (Wang, S. E. et al, 2007), it is presently unclear whether IKK engages SMADs to repress the gene in prostate cancer cells. Nevertheless, IKK is definitely involved in the control of TGF-SMAD target genes (Descargues et al, 2008a;Descargues et al, 2008b;Marinari et al, 2008).…”

Section: Fig 4 Tgf-dependent Downregulation Of E-cadherin Is Nfb-mentioning

confidence: 74%

IKKα controls canonical TGFβ–SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in Panc1 cells

Brandl

Seidler

Haller

et al. 2010

Journal of Cell Science

115

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There was an error published in J. Cell Sci. 123, 4231-4239.In Fig. 4A, the cRel siRNA western blot panel was inadvertently constructed using the wrong images and all three western blots showed incorrect loading controls. The correct images and loading controls are shown in the figure below. The mistake in the figure did not affect the conclusions of the paper.We apologise for this mistake. . TGFb-dependent downregulation of E-cadherin is NFkB-independent. (A) Panc1 cells were transfected with a control or RelA/p65-, RelB-or c-Relspecific siRNA. At 24 hours after the transfection, cells were treated with 10 ng/ml TGFb or were left as an untreated control in DMEM without FCS. After an additional 48 hours, western blots detected RelA/p65, RelB or c-Rel and E-cadherin expression. The membrane was stripped and probed for a-tubulin or b-actin to ensure equal protein loading. (B) Panc1 (upper graph) and MDA-MB231 cells (lower graph) cells were co-transfected with a control or IKKa-specific siRNA and 500 ng of the pGL3control-, NFkB-or SMAD-luciferase reporter gene constructs as indicated. At 24 hours after the transfection, cells were treated with 10 ng/ml TGFb or were left as an untreated control. Luciferase activity was measured 6 hours after the TGFb treatment (Student's t-test: *P,0.05 versus control). (C) Panc1 (upper graph) and MDA-MB231 (lower graph) cells were transfected with a control or IKKa-specific siRNA. At 48 hours after the transfection, cells were stimulated with TGFb (10 ng/ml) for 20 minutes and binding of SMAD3 and SMAD4 to a SMAD consensus oligonucleotide was detected using ABCD assays. Input represents 5% of whole-cell extract of control siRNA-transfected cells. (D) Panc1 cells were treated as in C. Immunoprecipitation was performed with an IKKa-specific antibody or pre-immune serum as a control. Western blots of immunoprecipitates were probed with antibodies against IKKa and SMAD3. Input represents 5% of whole-cell extract of control siRNA-transfected Panc1 cells. (E) MDA-MB231 cells were transfected with a control or IKKa-specific siRNA. At 24 hours after the transfection, cells were treated with 10 ng/ml TGFb or were left as an untreated control in DMEM without FCS. After an additional 48 hours, western blots detected IKKa expression. The membrane was stripped and probed for b-actin to ensure equal protein loading.

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Section: Fig 4 Tgf-dependent Downregulation Of E-cadherin Is Nfb-mentioning

confidence: 74%

IKKα controls canonical TGFβ–SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in Panc1 cells

Brandl

Seidler

Haller

et al. 2010

Journal of Cell Science

115

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“…Interestingly, other proteins and signaling pathways related to maspin regulation were reported to be dependent on p53. Transforming growth factor β (TGFβ) was also found to increase maspin expression and required wild-type p53 activity [18]. This work demonstrated two p53 binding sites in the maspin promoter that were either in close proximity or overlapped with a Smad binding element, leading to recruitment of Smad2/3 and p53 to the maspin promoter following TGFβ signaling.…”

Section: Regulation Of Maspin Expressionmentioning

confidence: 95%

“…Early studies demonstrate abundance of tyrosine phosphorylation in both endogenously expressed maspin in normal epithelial cells and after induction of maspin in transfected tumor cells [18]. Although the kinases responsible for this phosphorylation have yet to be identified, incubation of rMaspin with the TKD38 EGFR kinase domain led to tyrosine phosphorylation in a cell-free system.…”

Section: Regulation Of Maspin Expressionmentioning

confidence: 99%

Maspin Expression and its Metastasis Suppressing Function in Prostate Cancer

Shankar¹,

Candamo²,

MacLennan³

et al. 2016

Prostate Cancer - Leading-Edge Diagnostic Procedures and Treatments

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Mammary Serine Protease Inhibitor (Maspin) is a unique member of the serpin family with tumor suppressive properties. Maspin is a secreted protein encoded by a class II tumor suppressor gene, expressed in normal prostate luminal and basal cells but reduced or absent in prostate cancer. Currently, there is a consensus that maspin expression in prostate cancer is an indicator of a better prognosis and is a predictive marker for therapeutic response in prostate cancer. Experimental evidence consistently indicates that maspin suppresses tumor growth, invasion, and metastasis and promotes apoptosis in cancer cells. In this chapter, we discuss regulation of maspin expression, binding partners of maspin, and pathways through which maspin exerts its tumor suppressive properties. In addition, we summarize the progress that investigators have made in clarifying the role of maspin in prostate cancer biology and in assessing its role as a diagnostic marker and therapeutic agent.

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“…Cell fractionation, IP, and Western blotting were carried out as described previously (44,46). To pull down GTP-bound (active) Ran GTPase, His-tagged RanBP1 recombinant protein (Cytoskeleton Inc., Denver, CO) precoupled to His Mag Sepharose Ni magnetic beads (GE Healthcare, Piscataway, NJ) was utilized to pull down active Ran from the nuclear and cytoplasmic fractions as described previously (3).…”

Section: Methodsmentioning

confidence: 99%

Nuclear Translocation of Type I Transforming Growth Factor β Receptor Confers a Novel Function in RNA Processing

Chandra

Zang

et al. 2012

Molecular and Cellular Biology

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kSignaling of transforming growth factor ␤ (TGF-␤) is redirected in cancer to promote malignancy, but how TGF-␤ function is altered in a transformed cell is not fully understood. We investigated TGF-␤ signaling by profiling proteins that differentially bound to type I TGF-␤ receptor (T␤RI) in nontransformed, HER2-transformed, and HER2-negative breast cancer cells using immunoprecipitation followed by protein identification. Interestingly, several nuclear proteins implicated in posttranscriptional RNA processing were uniquely identified in the T␤RI coprecipitates from HER2-transformed cells. Ligand-inducible nuclear translocation of T␤RI was observed only in transformed cells, and the translocation required importin ␤1, nucleolin, and Smad2/3. This trafficking was dependent on the high Ran GTPase activity resulting from oncogenic transformation. In the nucleus, T␤RI associated with purine-rich RNA sequences in a synergistic manner with the RNA-binding factor hnRNP A1. We further found that nuclear translocation of T␤RI specifically induced epidermal growth factor receptor (EGFR) transcript isoform c, which encodes a soluble EGFR protein, through alternative splicing or 3=-end processing. Our study confirms a cancerspecific nuclear translocation of T␤RI and demonstrates its potential function in regulating nuclear RNA processing, as well as a novel gain-of-function mechanism of TGF-␤ signaling in cancer.

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Convergence of p53 and Transforming Growth Factor β (TGFβ) Signaling on Activating Expression of the Tumor Suppressor Gene maspin in Mammary Epithelial Cells

Cited by 35 publications

References 38 publications

IKKα controls canonical TGFβ–SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in Panc1 cells

IKKα controls canonical TGFβ–SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in Panc1 cells

Maspin Expression and its Metastasis Suppressing Function in Prostate Cancer

Nuclear Translocation of Type I Transforming Growth Factor β Receptor Confers a Novel Function in RNA Processing

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