Search results for PPM1A

Showing 8 results out of 8

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Species

Types

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Protein (2 results from a total of 2)

Identifier: R-HSA-205813
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: PPM1A: P35813
Identifier: R-HSA-380928
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: PPM1A: P35813

Reaction (3 results from a total of 3)

Identifier: R-HSA-209055
Species: Homo sapiens
Compartment: nucleoplasm
In the nucleus, protein type 2C phosphatase, PPM1A, dephosphorylates SMAD2 and SMAD3, resulting in dissociation of SMAD2/3:SMAD4 heterotrimeric complexes.
Identifier: R-HSA-2187388
Species: Homo sapiens
Compartment: nucleoplasm
PPM1A protein phosphatase binds phosphorylated SMAD2 and SMAD3 in the nucleus.
Identifier: R-HSA-2187395
Species: Homo sapiens
Compartment: cytosol, nucleoplasm
After dephosphorylation by PPM1A, SMAD2 and SMAD3 translocate to the cytosol.

Complex (1 results from a total of 1)

Identifier: R-HSA-2187392
Species: Homo sapiens
Compartment: nucleoplasm

Pathway (2 results from a total of 2)

Identifier: R-HSA-2173793
Species: 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 ubiquitin ligases (Lin et al. 2006, Dupont et al. 2009).
Identifier: R-HSA-2173795
Species: 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 al. 1999, Sun et al. 1999 PNAS, Bonni et al. 2001) through recruitment of SMURF2 (Bonni et al. 2001) or RNF111 i.e. Arkadia (Levy et al. 2007) ubiquitin ligases to SKI/SKIL by SMAD2/3. Therefore,the ratio of SMAD2/3 and SKI/SKIL determines the outcome: inhibition of SMAD2/3:SMAD4-mediated transcription or degradation of SKI/SKIL. SKI and SKIL are overexpressed in various cancer types and their oncogenic effect is connected with their ability to inhibit signaling by TGF-beta receptor complex.
SMAD4 can be monoubiquitinated by a nuclear ubiquitin ligase TRIM33 (Ecto, Ectodermin, Tif1-gamma). Monoubiquitination of SMAD4 disrupts SMAD2/3:SMAD4 heterotrimers and leads to SMAD4 translocation to the cytosol. In the cytosol, SMAD4 can be deubiquitinated by USP9X (FAM), reversing TRIM33-mediated negative regulation (Dupont et al. 2009).
Phosphorylation of the linker region of SMAD2 and SMAD3 by CDK8 or CDK9 primes SMAD2/3:SMAD4 complex for ubiquitination by NEDD4L and SMURF ubiquitin ligases. NEDD4L ubiquitinates SMAD2/3 and targets SMAD2/3:SMAD4 heterotrimer for degradation (Gao et al. 2009). SMURF2 monoubiquitinates SMAD2/3, leading to disruption of SMAD2/3:SMAD4 complexes (Tang et al. 2011).
Transcriptional repressors TGIF1 and TGIF2 bind SMAD2/3:SMAD4 complexes and inhibit SMAD-mediated transcription by recruitment of histone deacetylase HDAC1 to SMAD-binding promoter elements (Wotton et al. 1999, Melhuish et al. 2001).
PARP1 can attach poly ADP-ribosyl chains to SMAD3 and SMAD4 within SMAD2/3:SMAD4 heterotrimers. PARylated SMAD2/3:SMAD4 complexes are unable to bind SMAD-binding DNA elements (SBEs) (Lonn et al. 2010).
Phosphorylated SMAD2 and SMAD3 can be dephosphorylated by PPM1A protein phosphatase, leading to dissociation of SMAD2/3 complexes and translocation of unphosphorylated SMAD2/3 to the cytosol (Lin et al. 2006).
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