Crosstalk from Notch signaling pathway to TGF-beta signaling pathway

List of curated literature with evidence for crosstalk from Notch signaling pathway to TGF-beta signaling pathway

  • Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3.

    • PubMed ID : 14638857
    • Molecule in Notch signaling pathway: NOTCH-1
    • Species : Gallus gallus
    • Transcription : yes

    • Molecule in TGF-beta signaling pathway: SMAD3
    • Tissue : embryo
    • Regulation type : Activating
    • Sentence from paper : In a reciprocal situation, our observations suggest a mechanism by which Notch signaling could influence the expression of TGF-B target genes.

  • Notch activation on effector T cells increases their sensitivity to Treg cell-mediated suppression through upregulation of TGF-βRII expression.

    • PubMed ID : 22585622
    • Molecule in Notch signaling pathway: NOTCH1
    • Species : Homo sapiens
    • Transcription : no

    • Molecule in TGF-beta signaling pathway: SMAD3
    • Tissue : T-lymphocyte
    • Regulation type : Activating
    • Sentence from paper : Notch signaling plays an important role on effector function of TGF-β and its signaling through an interaction of NICD and Smad 3

  • Notch activation on effector T cells increases their sensitivity to Treg cell-mediated suppression through upregulation of TGF-βRII expression.

    • PubMed ID : 22585622
    • Molecule in Notch signaling pathway: HES1
    • Species : Homo sapiens
    • Transcription : yes

    • Molecule in TGF-beta signaling pathway: TGFBR2
    • Tissue : T-lymphocyte
    • Regulation type : Activating
    • Sentence from paper : Here, we found that HES, the main transcription factor donwstream of Notch, induced a strong transactivation of TGF-ßRII by binding the TGF-βRII promoter through its DNA-binding activity

  • Notch activation on effector T cells increases their sensitivity to Treg cell-mediated suppression through upregulation of TGF-βRII expression.

    • PubMed ID : 22585622
    • Molecule in Notch signaling pathway: HES1
    • Species : Homo sapiens
    • Transcription : yes

    • Molecule in TGF-beta signaling pathway: TGFBR2
    • Tissue : T-lymphocyte
    • Regulation type : Activating
    • Sentence from paper : We demonstrate that HES (hairy and enhancer of split), the main transcription factor downstream of Notch, induces strong transactivation of TGF-BRII by binding the TGF-BRII promoter through its DNA-binding domain.

  • Tumor-infiltrating myeloid cells activate Dll4/Notch/TGF-β signaling to drive malignant progression.

    • PubMed ID : 24520074
    • Molecule in Notch signaling pathway: Notch1/Notch4
    • Species : Mus musculus
    • Transcription : no
    • Sentence from paper : Heightened Dll4/Notch signaling in tumor cells magnified TGF-β-induced pSMAD2/3 signaling and was required to sustain TGF-β-induced tumor cell growth.

  • Tumor-infiltrating myeloid cells activate Dll4/Notch/TGF-β signaling to drive malignant progression.

    • PubMed ID : 24520074
    • Molecule in Notch signaling pathway: NOTCH1
    • Species : Homo sapiens
    • Transcription : no

    • Molecule in TGF-beta signaling pathway: SMAD2
    • Tissue : RCC 786-O cell
    • Regulation type : Activating
    • Sentence from paper : Notch signaling modulates expression of BMP family members and TGF-β target genes

Molecules mediating the crosstalk
Molecule in Notch signaling pathwayMolecule in TGF-beta signaling pathwayTissueSpeciesPubMed Identifier
NOTCH-1SMAD3embryoGallus gallus14638857
NOTCH1SMAD3T-lymphocyteHomo sapiens22585622
HES1TGFBR2T-lymphocyteHomo sapiens22585622
HES1TGFBR2T-lymphocyteHomo sapiens22585622
Notch1/Notch4Smad2:Smad3marrow cellMus musculus24520074
NOTCH1SMAD2RCC 786-O cellHomo sapiens24520074

Note: "Unknown" indicates that the molecule has not been identified.

Note: We direct each interaction from the molecule in the first pathway to the molecule in the second pathway. The direction of the interaction does not imply that the first molecule regulates the second molecule or that they directly interact. Hence, the interactions in this network may be indirect and may not indicate any mechanism.

Attribute NameDescription
Pathway A

The name of the upstream (first) pathway in a pair of crosstalking pathways.

Pathway B

The name of the downstream (second) pathway in a pair of crosstalking pathways.

Pubmed Query

The string used as a structured query in PubMed that returned the recorded PMID as a result.

PMID

The PubMed identifier for the reported publication.
We recorded "NO_RESULTS_FOR_PUBMED_QUERY" as a dummy PMID when the PubMed query returned no results.

Crosstalk

yes, if Pathway A elicits a downstream transcriptional response in Pathway B.
no, otherwise.

Transcriptional

yes, if the crosstalk is transcriptional.
no, otherwise.

Regulation type

The downstream effect on Pathway B. This attribute can take one of the following two values:

  • Activating: Stimulation of Pathway A up-regulates a gene or activates a protein that is representative of Pathway B.
  • Inhibiting: Stimulation of Pathway A down-regulates a gene or inhibits a protein that is representative of Pathway B.
Molecule A*

The molecule in Pathway A responsible for mediating crosstalk to Pathway B.

Molecule A Identifier

Unique identifier for Molecule A in the namespace recorded in "Molecule A Source", e.g., the UniProt ID of a protein.

Molecule A Source

The name of database that the value in "Molecule A Identifier" comes from, e.g., "UniProt" if the molecule is a protein.

Molecule B*

The molecule in Pathway B responsible for mediating crosstalk from Pathway A.

Molecule B Identifier

Unique identifier for Molecule B in the namespace recorded in "Molecule B Source", e.g., the UniProt ID of a protein.

Molecule B Source

The name of database that the value in "Molecule B Identifier" comes from, e.g., "UniProt" if the molecule is a protein.

Species

The name of the species in which the crosstalk was observed.

Tissue

The name of the tissue or cell line in which the crosstalk was observed.

BTO ID

The BRENDA Tissue Ontology (BTO) Identifier of the tissue or cell line in which the crosstalk was observed.

Condition

Notes on the experimental condition in the publication.

Sentence from paper

The sentence in the publication supporting the crosstalk. We record a sentence only if it states that Pathway A increases or decreases Pathway B signaling. The sentence may also include information about the proteins or genes responsible for mediating the crosstalk.

Misleading evidence for crosstalk

A sentence in the paper that appears to support evidence for crosstalk when the study does not conclude there is crosstalk.

Additional notes

A curator's notes that may provide rationale for the values recorded for the attributes.

*This attribute may represent either an individual molecule or several molecules. We use the following syntax for this attribute.

  • colon (:): The molecules participate in the complex, e.g., SMAD3:SMAD4 in the case of crosstalk from the TGF-beta signaling pathway to the Hippo signaling pathway (the complex consisting of SMAD3 and SMAD4 mediates this crosstalk).
  • slash (/): Either of the molecules can mediate the crosstalk, e.g., YAP1/WWTR1 for the same pair of pathways (YAP1 or WWTR1 can mediate the crosstalk).
  • comma (,): All the molecules are required for the crosstalk but they do not form a complex, e.g., TSC2,RPTOR for the crosstalk from the MAPK signaling pathway to the mTOR signaling pathway (both TSC2 and RPTOR act as mediators).
  • brackets ([]): If we cannot identify the specific molecule, we record all molecules in the family, e.g., [TEAD1/TEAD2/TEAD3/TEAD4]. In this case, the publication only listed the protein TEAD as mediating the crosstalk (from the Hippo signaling pathway to the Wnt signaling pathway).