TIAM 1(21q22.11) Rac-1 spedifinen GEF (guanosiininukleotidien vaihtotekijä)

 TIAM1
https://www.ncbi.nlm.nih.gov/gene/7074 

Also known as

TIAM-1

Summary

This gene encodes a RAC1-specific guanine nucleotide exchange factor (GEF). GEFs mediate the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP). The binding of GTP induces a conformational change in RAC1 that allows downstream effectors to bind and transduce a signal. This gene thus regulates RAC1 signaling pathways that affect cell shape, migration, adhesion, growth, survival, and polarity, as well as influencing actin cytoskeletal formation, endocytosis, and membrane trafficking. This gene thus plays an important role in cell invasion, metastasis, and carcinogenesis.

 In addition to RAC1, the encoded protein activates additional Rho-like GTPases such as CDC42, RAC2, RAC3 and RHOA.  

This gene encodes multiple protein isoforms that experience a diverse array of intramolecular, protein-protein, and phosphorylation interactions as well as phosphoinositide (PI)  binding. Both the longer and shorter isoforms have C-terminal Dbl homology (DH) and pleckstrin homology (PH) domains while only the longer isoforms of this gene have the N-terminal myristoylation site and the downstream N-terminal PH domain, ras-binding domain (RBD), and PSD-95/DlgA/ZO-1 (PDZ) domain. [provided by RefSeq, Jul 2017]

Expression

Broad expression in esophagus (RPKM 7.7), skin (RPKM 6.8) and 23 other tissues See more

Orthologs

mouse all

Preferred Names

T-lymphoma invasion and metastasis-inducing protein 1

Names

T cell lymphoma invasion and metastasis 1

human T-lymphoma invasion and metastasis inducing TIAM1 protein

https://www.sciencedirect.com/science/article/abs/pii/S0898656813002532
Metformiini ja TIAM-1

Related articles in PubMed

1. Competition between TIAM1 and Membranes Balances Endophilin A3 Activity in Cancer Metastasis. Poudel KR, et al. Dev Cell, 2018 Jun 18. PMID 29920278, Free PMC Article
2. Upregulation of Tiam1 contributes to cervical cancer disease progression and indicates poor survival outcome. Yang Y, et al. Hum Pathol, 2018 May. PMID 29452216
3. The Tiam1 guanine nucleotide exchange factor is auto-inhibited by its pleckstrin homology coiled-coil extension domain. Xu Z, et al. J Biol Chem, 2017 Oct 27. PMID 28882897, Free PMC Article
4. Expression of T-lymphoma invasion and metastasis factor on the occurrence of oral squamous cell carcinoma. Song B, et al. J Biol Regul Homeost Agents, 2017 Apr-Jun. PMID 28685528
5. TIAM1 variants improve clinical outcome in neuroblastoma. Sanmartín E, et al. Oncotarget, 2017 Jul 11. PMID 28423360, Free PMC Article

See all (157) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

1. our study demonstrated that upregulation of Tiam1 contributes to cervical cancer disease progression and indicates poor survival outcome
2. Overexpression of miR-10b in HeLa and SiHa suppressed cell proliferation, migration and invasion, and induced apoptosis and miR-10b downregulation had opposite effects. Mechanistically, T-cell lymphoma invasion and metastasis 1 (Tiam1) was identified as a direct and functional target of miR-10b.
3. Study in hepatocellular carcinoma (HCC) cells proves that SETDB1 promotes the proliferation and migration of cells by forming SETDB1-Tiam1 compounds. SETDB1-Tiam1 compounds were involved in a novel pathway, which regulated epigenetic modification of gene expression in HCC patients samples.
4. Down-regulating Tiam1 expression resulted in the down-regulation of circRNA-ACAP2 expression and up-regulation of miR-21-5P expression.
5. The effects of Tiam1 on metastasis and EMT mediated by the Wnt/beta-catenin pathway were reversed by Rac1 silencing, suggesting that the prometastatic effect of Tiam1 is mediated by the activation of Rac1. These results indicate that Tiam1 may be a prognostic factor and potential therapeutic target for the treatment of thyroid cancers.
6. These findings highlight a regulatory pathway of Tiam1/Rac1 in Th17 cells and suggest that it may be a therapeutic target in multiple sclerosis.
7. Competing interactions of EndoA3 with membrane versus TIAM1 modulate hyperproliferative and metastatic phenotypes. Disruption of EndoA3-membrane interactions stimulates TIAM1 and small GTPases in vitro, and further promotes pro-metastatic phenotypes in vivo.
8. PDZ domains direct protein-protein interactions and serve as models for protein design. This study optimized a protein design energy function for the Tiam1 and Cask PDZ domains that combines a molecular mechanics energy, Generalized Born solvent, and an empirical unfolded state model.
9. Clinical outcome was improved in tumors where a TIAM1 variant was present concomitantly with either ALK mutation or MYCN amplification.
10. the Ser179Glu mutant of SDC-4 binds strongly Tiam1, a Rac1-GEF reducing Rac1-GTP by 3-fold in MCF-7 breast adenocarcinoma cells.