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CDKN1A — MYC

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: CDKN1A → Complex of HIF1A-MYC (increases)
  Evidence: a study using HCT116 colon carcinoma cells depleted of either p53 or p21 found that HIF1? is required for cellcycle arrest through the induction of p21 by a direct interaction between HIF1? and MYC39.
• NCI Pathway Database p73 transcription factor network: TAp73a (tetramer)/MYC complex (TP73-MYC) → p21CIP1 (CDKN1A) (transcription, inhibits) Lee et al., Oncogene 1999*, Costanzo et al., Mol Cell 2002, Watanabe et al., J Biol Chem 2002*, Fontemaggi et al., J Biol Chem 2002*
  Evidence: reporter gene

Text-mined interactions from Literome

Mitchell et al., Cell Growth Differ 1999 (Breast Neoplasms...) : Overexpression of c-Myc inhibits p21WAF1/CIP1 expression and induces S-phase entry in 12-O-tetradecanoylphorbol-13-acetate ( TPA ) -sensitive human cancer cells ... Overexpression of c-Myc reduced the levels of endogenous p21 mRNA, and transfection of c-Myc repressed p21-promoter luciferase-reporter gene expression
Kitaura et al., J Biol Chem 2000 : These results suggest that c-Myc activates DNA replication via inactivation of p21 and that p21 , vice versa, represses the transcriptional activity of c-Myc
Claassen et al., Proc Natl Acad Sci U S A 2000 : A role for transcriptional repression of p21CIP1 by c-Myc in overcoming transforming growth factor beta -induced cell-cycle arrest ... Repression of p21 ( CIP1 ) transcription by c-Myc occurred at the promoter level in a region near the start site of transcriptional initiation and was independent of histone deacetylase activity
Gartel et al., Proc Natl Acad Sci U S A 2001 : Myc represses the p21 ( WAF1/CIP1 ) promoter and interacts with Sp1/Sp3 ... Recent studies showed that Myc can repress p21 transcription, thereby overriding a p21 mediated cell cycle checkpoint ... We found that activation of a Myc-estrogen receptor fusion protein by 4-hydroxytamoxifen in mouse cells resulted in suppression of endogenous p21 transcription ... In transient transfection studies, Myc effectively repressed p21 promoter constructs containing only 119 bp of sequence upstream of the transcription start site
Herold et al., Mol Cell 2002 : Using both c-myc ( -/- ) cells and a point mutant of Myc that is deficient in Miz-1 dependent repression, we show that Myc negatively regulates transcription of p21Cip1 upon UV irradiation and facilitates recovery from UV-induced cell cycle arrest through binding to Miz-1
Wu et al., Oncogene 2003 : Myc represses differentiation induced p21CIP1 expression via Miz-1 dependent interaction with the p21 core promoter ... We show here that Myc represses differentiation induced expression of the cyclin dependent kinase (CDK) inhibitor p21CIP1 ( CDKN1A, p21 ), known to play an important role in cell fate decisions during growth and differentiation, in hematopoietic cells ... Using mutants of c-Myc with impaired binding to Miz-1, our results further show that repression of p21 promoter/reporters as well as the endogenous p21 gene by Myc depends on interaction with Miz-1
Horiguchi-Yamada et al., Anticancer Res 2002 : DNA topoisomerase II inhibitor, etoposide, induces p21WAF1/CIP1 through down-regulation of c-Myc in K562 cells ... p21 promoter activity was repressed by c-Myc in proliferating K562 cells, and detoposide induced down-regulation of c-Myc released this suppression, resulting in the induction of p21
Gartel et al., Exp Cell Res 2003 (Cell Transformation, Neoplastic) : Myc suppresses expression of cell cycle/growth arrest genes gas1, p15, p21 , p27, and gadd34, -45, and -153
Löhr et al., J Biol Chem 2003 : Overexpressed c-Myc reduced the transcription of p21/CDKN1A and impaired p53 mediated repression but did not abolish repression by ectopic p21
Vaqué et al., J Biol Chem 2005 (Leukemia...) : However, mutational analysis of the p21 promoter and the use of a Gal4-Sp1 chimeric protein strongly suggest that c-Myc affects Sp1 transcriptional activity but not the binding of Sp1 to the p21 promoter
Brenner et al., EMBO J 2005 : Finally, we show that DNA methylation is required for Myc mediated repression of p21Cip1
Mukherjee et al., J Biol Chem 2005 (Breast Neoplasms) : Using RNA interference to suppress c-Myc expression, we further established that c-Myc is required for estrogen mediated decreases in p21 ( WAF1/CIP1 ) ... The p21 levels in the antiestrogen-resistant cells increased when c-Myc expression was suppressed, suggesting that loss of p21 regulation was a consequence of constitutive c-Myc expression
Mack et al., Mol Cell Biol 2005 (Fibrosarcoma) : The transcription of p21 and p27 is inhibited by c-Myc ; therefore, the induction of CKIs was attributed to the ability of HIF to antagonize c-Myc activity
Liu et al., Biochem J 2006 : Polyamine modulated c-Myc expression in normal intestinal epithelial cells regulates p21Cip1 transcription through a proximal promoter region ... Experiments using different p21Cip1 promoter mutants showed that transcriptional repression of p21Cip1 by c-Myc was mediated through Miz-1- and Sp1 binding sites within the proximal region of the p21Cip1 promoter in normal IECs
Oskarsson et al., Genes Dev 2006 (Cell Transformation, Neoplastic...) : This identifies c-Myc mediated repression of p21 ( Cip1 ) as a key step for Ras-driven epidermal tumorigenesis
Onwuegbusi et al., PloS one 2007 (Adenocarcinoma...) : 4/5 adenocarcinoma cell lines failed to cell cycle arrest, down-regulate c-Myc or induce p21 in response to TGFbeta, and modulation of a Smad3/4 specific promoter was inhibited
Lim et al., Cancer Res 2008 : Moreover, HIF-1alpha disruption of hARD1/beta-catenin repressed TCF4 activity, resulting in c-Myc suppression and p21 ( cip1 ) induction
Jung et al., Cell cycle (Georgetown, Tex.) 2009 (Neoplasms) : Recently, we reported a novel mechanism which allows c-MYC to repress p21 : c-MYC triggers a transcriptional cascade by directly inducing the gene encoding the bHLH-LZ transcription factor AP4 (TFAP4), which binds to recognition motifs located in the vicinity of the p21 promoter and mediates transcriptional repression of p21
Wang et al., Int J Oncol 2010 : In the study presented here, we compared p21 mRNA in the nucleus and cytoplasm of c-Myc stable transfectants with its control, which indicated further repression of p21 by c-Myc at the post-transcriptional level ... These results suggest c-Myc could further repress p21 expression at the post-transcriptional level through some, but not all, members of miR-17 family
Muñoz-Alonso et al., J Cell Physiol 2012 (Polyploidy) : Protooncogene MYC induces cell growth and proliferation, inhibits differentiation and represses p21 ( CIP )
Wong et al., Mol Cell Biol 2012 : Silencing of TFAP2C-KDM5B-Myc led to increased H3K4me3 at the endogenous promoter and full induction of CDKN1A expression
Chou et al., Cell Death Differ 2012 : Moreover, CITED2 inhibited cellular quiescence by enhancing MYC mediated suppression of p21 ( CIP1 )
Inoue et al., Genes Dev 2013 (Cell Transformation, Neoplastic...) : Mule/Huwe1/Arf-BP1 suppresses Ras-driven tumorigenesis by preventing c-Myc/Miz1 mediated down-regulation of p21 and p15 ... Notably, in the absence of Mule, c-Myc/Miz1 transcriptional complexes accumulated, and levels of p21CDKN1A ( p21 ) and p15INK4B ( p15 ) were down-regulated
Jackstadt et al., Cell death & disease 2013 (Cell Transformation, Neoplastic) : Activation of c-MYC resulted in repression of p21 and p16 in AP4 ( +/+ ), but not in AP4 ( -/- ) MEFs
Malliri et al., Cell Growth Differ 1996 (Carcinoma, Squamous Cell) : Sensitivity to transforming growth factor beta 1-induced growth arrest is common in human squamous cell carcinoma cell lines : c-MYC down-regulation and p21waf1 induction are important early events ... However, in TGF-beta 1-resistant subclones of sensitive mycER expressing cells, p21waf1 was not induced , whereas both c-MYC and mycER protein levels decreased following TGF-beta 1 treatment