RAC1

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Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)
Protein RAC1 PDB 1ds6.png
PDB rendering based on 1ds6.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols RAC1 ; Rac-1; TC-25; p21-Rac1
External IDs OMIM602048 MGI97845 HomoloGene69035 ChEMBL: 6094 GeneCards: RAC1 Gene
RNA expression pattern
PBB GE RAC1 208640 at tn.png
PBB GE RAC1 208641 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5879 19353
Ensembl ENSG00000136238 ENSMUSG00000001847
UniProt P63000 P63001
RefSeq (mRNA) NM_006908 NM_009007
RefSeq (protein) NP_008839 NP_033033
Location (UCSC) Chr 7:
6.41 – 6.44 Mb
Chr 5:
143.51 – 143.53 Mb
PubMed search [1] [2]

Rac1, also known as Ras-related C3 botulinum toxin substrate 1 is a protein found in human cells. It is encoded by the RAC1 gene.[1][2] This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.[3]

Function[edit]

Rac1 is a small (~21 kDa) signaling G protein (more specifically a GTPase), and is a member of the Rac subfamily of the family Rho family of GTPases. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.[4]

Rac1 is a pleiotropic regulator of many cellular processes, including the cell cycle, cell-cell adhesion, motility (through the actin network), and of epithelial differentiation (proposed to be necessary for maintaining epidermal stem cells).

Role in cancer[edit]

Along with other subfamily of Rac and Rho proteins, they exert an important regulatory role specifically in cell motility and cell growth. Rac1 has ubiquitous tissue expression, and drives cell motility by formation of lamellipodia.[5] In order for cancer cells to grow and invade local and distant tissues, deregulation of cell motility is one of the hallmark events in cancer cell invasion and metastasis.[6] Activating or gain-of-function mutations of Rac1 are shown to play active roles in promoting mesenchymal-type of cell movement assisted by NEDD9 and DOCK3 protein complex.[7] Such abnormal cell motility may result in epithelial mesenchymal transition (EMT) – a driving mechanism for tumor metastasis as well as drug-resistant tumor relapse.[8][9]

Clinical significance[edit]

Activating mutations in Rac1 have been recently discovered in large-scale genomic studies involving melanoma [10][11][12] and non-small cell lung cancer.[13] As a result, Rac1 is considered a therapeutic target for many of these diseases.[14]

A few recent studies have also exploited targeted therapy to suppress tumor growth by pharmacological inhibition of Rac1 activity in metastatic melanoma and liver cancer as well as in human breast cancer.[15][16][17] For example, Rac1-dependent pathway inhibition resulted in the reversal of tumor cell phenotypes, suggesting Rac1 as a predictive marker and therapeutic target for trastuzumab-resistant breast cancer.[16]

Interactions[edit]

RAC1 has been shown to interact with:


References[edit]

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  2. ^ Jordan P, Brazåo R, Boavida MG, Gespach C, Chastre E (November 1999). "Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors". Oncogene 18 (48): 6835–9. doi:10.1038/sj.onc.1203233. PMID 10597294. 
  3. ^ Zhou C, Licciulli S, Avila JL, Cho M, Troutman S, Jiang P, Kossenkov AV, Showe LC, Liu Q, Vachani A, Albelda SM, Kissil JL (February 2013). "The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis". Oncogene 32 (7): 903–9. doi:10.1038/onc.2012.99. PMC 3384754. PMID 22430205. 
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  5. ^ Parri M, Chiarugi P. (2010). "Rac and Rho GTPases in cancer cell motility control". Cell communication and signaling. 8 (23). 
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  7. ^ Sanz-Moreno V, Gadea G, Ahn J, Paterson H, Marra P, Pinner S, et al. (Oct 31, 2008). "Rac activation and inactivation control plasticity of tumor cell movement.". Cell. 135 (3): 510–523. 
  8. ^ Stallings-Mann ML, Waldmann J, Zhang Y, Miller E, Gauthier ML, Visscher DW, et al. (Jul 11, 2012). "Matrix metalloproteinase induction of Rac1b, a key effector of lung cancer progression.". Science translational medicine. 4 (142): 510–523. 
  9. ^ Yang WH, Lan HY, Huang CH, Tai SK, Tzeng CH, Kao SY, et al. (Apr 2012). "RAC1 activation mediates Twist1-induced cancer cell migration.". Nature cell biology. 14 (4): 366–374. 
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Further reading[edit]

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External links[edit]