Related Experiment Video
Updated: Jun 14, 2026
10:27
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
The Ras effector RASSF2 controls the PAR-4 tumor suppressor
Howard Donninger1, Luke Hesson, Michele Vos
1Department of Medicine, James Graham Brown Cancer Center, Molecular Targets Program, University of Louisville, 505 S. Hancock St., Louisville, KY 40202, USA.
Molecular and Cellular Biology
|April 7, 2010
Summary
The Ras association domain family protein 2 (RASSF2) acts as a tumor suppressor by interacting with prostate apoptosis response protein 4 (PAR-4). This interaction is crucial for RASSF2
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ras association domain family protein 2 (RASSF2) is a proapoptotic protein implicated as a tumor suppressor.
- Inhibition of RASSF2 expression promotes K-Ras-driven cell transformation.
- Epigenetic inactivation of RASSF2 is common in primary tumors with mutant Ras.
Purpose of the Study:
- To elucidate the mechanism of action of the RASSF2 tumor suppressor.
- To identify novel signaling pathways regulated by RASSF2.
- To explain the frequent inactivation of RASSF2 in prostate tumors.
Main Methods:
- Co-immunoprecipitation assays to detect protein-protein interactions.
- Western blotting to analyze protein expression and localization.
- Cellular fractionation and immunofluorescence microscopy to study protein translocation.
Main Results:
- RASSF2 directly complexes with the prostate apoptosis response protein 4 (PAR-4) tumor suppressor.
- K-Ras regulates the RASSF2-PAR-4 interaction, which is essential for PAR-4's apoptotic activity.
- RASSF2 modulates the nuclear translocation of PAR-4 in prostate cancer cells.
Conclusions:
- RASSF2 functions as a tumor suppressor by regulating PAR-4 nuclear localization and apoptotic signaling.
- This study identifies a novel mechanism of action for RASSF proteins.
- The findings provide a molecular explanation for RASSF2 inactivation in prostate tumorigenesis.
Related Concept Videos
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...