RSU1 Human (Ras Suppressor Protein 1) is a leucine-rich repeat (LRR)-containing protein encoded by the RSU1 gene. It plays critical roles in cellular signaling, adhesion, and cytoskeletal organization. Recombinant RSU1 Human is produced in Escherichia coli as a non-glycosylated protein with a molecular mass of ~33.9 kDa (1-277 amino acids) and includes a 23-amino acid N-terminal His-tag for purification .
| Property | Description |
|---|---|
| Amino Acid Sequence | 300 residues (1-277), fused with His-tag |
| Molecular Weight | ~33.9 kDa |
| Source | E. coli (recombinant) |
| Formulation | 20 mM Tris-HCl (pH 8.0), 0.4 M Urea, 10% Glycerol |
| Key Domains | LRR solenoid, PINCH1-binding motifs (LIM5 interaction) |
RSU1 forms a curved LRR solenoid structure that binds tightly to PINCH1’s LIM5 domain, blocking its actin-binding activity and inhibiting F-actin bundling . This interaction regulates focal adhesion (FA) dynamics and stress fiber formation .
RSU1 suppresses oncogenic Ras transformation by modulating downstream pathways. It interacts with PINCH1 and Integrin Linked Kinase (ILK) to integrate Ras and integrin signaling, controlling cell adhesion, migration, and apoptosis .
RSU1 inhibits the ILK/PINCH/Parvin (IPP) complex’s actin-bundling activity. Overexpression reduces stress fibers and impairs cell spreading, while PINCH1-binding mutants (e.g., Y140K) lose this inhibitory effect .
Isoform-Specific Effects:
RSU1L (Long Isoform): Depletion in MCF-7 breast cancer cells abolishes tumor spheroid invasion, while depletion in MDA-MB-231-LM2 cells increases invasion via RSU1-X1 compensation .
RSU1-X1 (Truncated Isoform): Upregulated in metastatic samples, promotes invasion in aggressive breast cancer subtypes .
| Cancer Type | Expression Trend | Functional Impact |
|---|---|---|
| Breast Cancer | RSU1L ↑ in metastatic samples | Invasion promotion via RSU1-X1 compensation |
| Hepatocellular | RSU1 gene loss observed | Tumorigenesis suppression |
| Colorectal | RSU1 mRNA ↑ in metastasis | Potential pro-metastatic role |
RSU1 modulates ethanol sensitivity and preference in Drosophila and humans:
Drosophila: Global RSU1 knockout reduces ethanol sedation sensitivity and increases naïve preference. Mushroom body (MB)-specific depletion abolishes acquired preference .
Humans: RSU1 polymorphisms correlate with ventral striatum activation during reward anticipation and alcohol dependence risk .
RSU1 regulates Rac1 GTPase activity and actin dynamics, critical for synaptic function and drug-related behavioral plasticity .
Ras Suppressor Protein 1 (RSU1) is a protein that plays a significant role in the Ras signal transduction pathway, which is crucial for various cellular processes including growth inhibition and differentiation. Initially identified for its ability to inhibit v-Ras transformation, RSU1 has been extensively studied in both mouse and human cell lines .
RSU1 was discovered as a suppressor of Ras-induced transformation, meaning it can inhibit the oncogenic activity of the Ras protein. Ras proteins are small GTPases that play a key role in cell proliferation, differentiation, and survival. Mutations in Ras genes are common in various cancers, making the study of RSU1 particularly important .
RSU1 localizes to cell-extracellular matrix adhesions, which are critical for cell migration and invasion. This localization suggests that RSU1 may play a role in regulating metastasis-related cellular processes .
Recent studies have provided detailed insights into the structure of RSU1 and its interaction with other proteins. RSU1 interacts with PINCH1, a component of the integrin-linked kinase (ILK)/PINCH/Parvin (IPP) complex, which is essential for focal adhesion formation and signaling. The interaction between RSU1 and PINCH1 negatively regulates F-actin bundling, thereby affecting cell adhesion and migration .
RSU1’s role in cancer has been a subject of significant research. Elevated expression of RSU1 has been observed in various cancer types, including breast, liver, and brain cancers. Its role in regulating metastasis-related processes, such as cell invasion and migration, is still being explored. However, in vitro studies have shown that RSU1 can impair stress fiber formation and cell spreading, indicating its potential as a therapeutic target .