Reactome: A Curated Pathway Database
Results 1 to 10 of 137
Pathways (34) Reactions (56) Proteins (3) Others (44)
Pathway: SMAD4 MH2 Domain Mutants in Cancer (Homo sapiens)
The MH2 domain of SMAD4 is the most frequently mutated SMAD4 region in cancer. MH2 domain mutations result in the loss of function of SMAD4 by abrogating the formation of transcriptionally active heterotrimers of SMAD4 and TGF-beta receptor complex-activated R-SMADs - SMAD2 and SMAD3 (Shi et al. 1997, Chacko et al. 2001, Chacko et al. 2004, Fleming et al. 2013). The hotspot MH2 domain amino acid
Last changed: 2014-11-21 14:40:22

Pathway: Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer (Homo sapiens)
In the nucleus, SMAD2/3:SMAD4 heterotrimer complex acts as a transcriptional regulator. The activity of SMAD2/3 complex is regulated both positively and negatively by association with other transcription factors (Chen et al. 2002, Varelas et al. 2008, Stroschein et al. 1999, Wotton et al. 1999). In addition, the activity of SMAD2/3:SMAD4 complex can be inhibited by nuclear protein phosphatases and ubiq
Last changed: 2014-11-21 14:40:22

Pathway: Loss of Function of SMAD4 in Cancer (Homo sapiens)
SMAD4 was identified as a gene homozygously deleted in ~30% of pancreatic cancers and was named DPC4 (DPC stands for deleted in pancreatic cancer). SMAD4 maps to the chromosomal band 18q21.1, and about 90% of pancreatic carcinomas show allelic loss at chromosomal arm 18q (Hahn et al. 1996), while ~50% of pancreatic cancers show some alteration of the SMAD4 gene (reviewed by Schutte et al. 1999).
Last changed: 2014-11-21 14:40:22

Pathway: SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription (Homo sapiens)
After phosphorylated SMAD2 and/or SMAD3 form a heterotrimer with SMAD4, SMAD2/3:SMAD4 complex translocates to the nucleus (Xu et al. 2000, Kurisaki et al. 2001, Xiao et al. 2003). In the nucleus, linker regions of SMAD2 and SMAD3 within SMAD2/3:SMAD4 complex can be phosphorylated by CDK8 associated with cyclin C (CDK8:CCNC) or CDK9 associated with cyclin T (CDK9:CCNT). CDK8/CDK9-mediated phosphorylatio
Last changed: 2014-11-21 14:40:22

Protein: UniProt:Q13485 SMAD4 (Homo sapiens)
Last changed: 2014-11-25 20:54:06

Pathway: Downregulation of SMAD2/3:SMAD4 transcriptional activity (Homo sapiens)
Transcriptional activity of SMAD2/3:SMAD4 heterotrimer can be inhibited by formation of a complex with SKI or SKIL (SNO), where SKI or SKIL recruit NCOR and possibly other transcriptional repressors to SMAD-binding promoter elements (Sun et al. 1999, Luo et al. 1999, Strochein et al. 1999). Higher levels of phosphorylated SMAD2 and SMAD3, however, may target SKI and SKIL for degradation (Strochein et a
Last changed: 2014-11-21 14:40:22

Pathway: Signal Transduction (Homo sapiens)
Signal transduction is a process in which extracellular signals elicit changes in cell state and act ... to formation of complexes of regulatory SMADs and SMAD4, which translocate to the nucleus where they act as transcription factors. WNT receptors transmit their signal through beta-catenin. In the absence of ligand, beta-catenin is constitutively degraded in a ubiquitin-dependent manner. WNT recept ...
Last changed: 2014-11-21 19:49:01

Pathway: Gene Expression (Homo sapiens)
Gene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are processed. Most annotation is centered on the generation of messenger RNAs (mRNAs) by regulated RNA polymerase II (PolII) transcription, although the activities of PolI and PolIII are also covered briefly, as are
Last changed: 2014-11-21 19:49:01

Pathway: Disease (Homo sapiens)
Biological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular viewpoint, human disease pathways have three mechanistic causes: the inclusion of microbially-expressed proteins, altered functions of human proteins, or changed expression levels of otherwise functionally
Last changed: 2014-11-21 19:49:01

Pathway: Developmental Biology (Homo sapiens)
As a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are aspects of the roles of cell adhesion molecules in axonal guidance and myogenesis, of transcriptional regulation in hematopoiesis (specifically, B lymphopoiesis), pancreatic beta cell and whit
Last changed: 2014-11-21 19:49:01

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