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Description

T-lymphoma invasion and metastasis-inducing protein 1 (UniProt Q13009, also known as TIAM-1) is encoded by the TIAM1 gene (Gene ID 7074) in human. TIAM-1 is a ubiquitously expressed guanine nucleotide exchange factor (GEF) that specifically activates the Rho-like GTPase Rac1 in response to growth factors and cell-substrate interaction. TIAM-1 associates with GTP-bound Ras and functions as an effector that mediates Rac activation by Ras. TIAM-1 promotes the formation of adherens junctions and the induction of an epithelial-like phenotype in mesenchymal cells, and is essential for the formation and maintenance of cadherin-based adhesions. Tiam1-knockdown in mice protects against Ras-induced skin carcinogenesis as a result of increased apoptosis and reduced proliferation/growth of keratinocytes. However, the fewer skin tumors developed progress more frequently to malignancy in Tiam1-knockout mice, indicating that loss of Tiam1 stimulates malignant conversion. Cellular TIAM-1 is targeted for proteasome-dependent degradation by the SCFbTrCP ubiquitin ligase in cooperation with casein kinase 1 and the MEK/ERK pathway upon mitogenic stimulation.