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CDKN1A — SMAD4
Pathways - manually collected, often from reviews:
Text-mined interactions from Literome
Pardali et al., J Biol Chem 2000
:
Role of
Smad proteins and transcription factor Sp1 in
p21 ( Waf1/Cip1 ) regulation by transforming growth factor-beta ... In this study we show that Smad3 and
Smad4 when overexpressed in HaCaT keratinocytes
lead to activation of the
p21 promoter ... Induction of the endogenous HaCaT p21 gene by TGF-beta1 is further enhanced after overexpression of Smad3 and Smad4, whereas dominant negative mutants of Smad3 and
Smad4 and the inhibitory Smad7 all
inhibit p21 induction by TGF-beta1 in a dose dependent manner
Iglesias et al., Oncogene 2000
(Carcinoma...) :
Smad4 mediates TGF-beta1 induced up-regulation of
p21Cip1 and growth arrest in MCA3D cells
Pouliot et al., J Endocrinol 2002
(Breast Neoplasms) :
Role of Smad1 and
Smad4 proteins in the induction of
p21WAF1,Cip1 during bone morphogenetic protein induced growth arrest in human breast cancer cells ...
p21 promoter activity
required both Smad1 and
Smad4 and was induced by either BMP-2 or constitutively active type I BMP receptors
Peng et al., Clin Cancer Res 2002
(Pancreatic Neoplasms) :
We seek to determine the
role of
Smad4/DPC4 in the suppression of tumor cell growth and in the regulation of TGF-beta mediated expression of cell-cycle regulatory genes p15(ink4b) and
p21 ( waf1 )
Ryu et al., Cancer Biol Ther 2003
(Breast Neoplasms...) :
Although
Smad4 dependent
CDKN1A/p21 induction represents the sole known effector of TGFbeta and activin tumor-suppressor effects, many downstream genes have not yet been evaluated for a suppressive role
Medrano et al., Oncogene 2003
(Melanoma...) :
SKI also facilitates cell-cycle progression by targeting the RB pathway by at least two ways : it directly associates with RB and represses its activity when expressed at high levels, and indirectly, it represses
Smad mediated induction of
p21 ( Waf-1 ) This results in increased CDK2 activity, RB phosphorylation, and inactivation
Pardali et al., J Cell Physiol 2005
:
Smad4 is
essential for
p21 regulation by all receptor pathways ... Based on the previously known ability of c-Myc to block p21 expression and epithelial growth arrest in response to TGF-beta1, we demonstrate that ectopic c-Myc expression can abrogate
Smad mediated
p21 induction by all TGF-beta and BMP receptors
Sonegawa et al., J Mol Med (Berl) 2007
(Carcinoma, Squamous Cell) :
In A431 cells, S100C/A11, Smad3, and
Smad4 were simultaneously transferred to the nuclei, and
p21 ( WAF1 ) was
induced upon exposure to TGFbeta
Kim et al., Arch Pharm Res 2007
:
Although it has been demonstrated that
p21WAF1/Cip1 could be induced by transforming growth factor-beta1 ( TGF-beta1 ) in a
Smad dependent manner, the cross-talk of Smad signaling pathway with other signaling pathways still remains poorly understood
Huang et al., Oncol Rep 2008
(Carcinoma, Hepatocellular...) :
Western blot analysis revealed that p16 was up-regulated and caspase 3 was activated by silencing of
Smad4 , and the expression of
p21 and wild-type p53 were not
affected
Lo et al., Molecular cancer 2010
:
In response to TGFbeta stimulation, LMP1 does not abolish
SMAD phosphorylation but
inhibits p21 protein expression
Wang et al., Gene 2011
(Carcinoma, Squamous Cell...) :
However in Ts cells stably expressing Smad4,
Smad4 mediated TGF-ß1 induced
p21 expression promoted cell apoptosis and inhibited cell proliferation, delayed MMP-2 expression, and decreased cell metastasis
Yilmaz et al., EMBO J 2011
(Melanoma, Experimental) :
Dlx2 counteracts TGFß induced cell-cycle arrest and apoptosis in mammary epithelial cells by at least two molecular mechanisms : Dlx2 acts as a direct transcriptional repressor of TGFß receptor II ( TGFßRII ) gene expression and reduces canonical,
Smad dependent TGFß signalling and expression of the cell-cycle inhibitor
p21 ( CIP1 ) and increases expression of the mitogenic transcription factor c-Myc
Moustakas et al., Proc Natl Acad Sci U S A 1998
:
Constitutive expression of
p21 was severely
reduced by a C-terminally truncated form of
Smad4 that was shown previously to block signaling through Smads ... Smad3/4 and to a much lesser extent
Smad2/4 caused high levels of transcriptional activation of the
p21 promoter
Hunt et al., Cancer Res 1998
(Carcinoma) :
Overexpression of the tumor suppressor gene
Smad4/DPC4 induces
p21waf1 expression and growth inhibition in human carcinoma cells ... Now we show that transient overexpression of
Smad4/DPC4 can
induce p21waf1 expression, specific Smad4 DNA binding activity, SBE4-luc reporter gene activity, and subsequent growth inhibition in Smad4/DPC4-null cells and other carcinoma cells in the presence or absence of TGF-beta