Related Experiment Video
Updated: May 29, 2026
08:35
Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
H-ras up-regulates expression of BNIP3
Wojciech Kalas1, Ewelina Swiderek, Andrzej Rapak
1Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. kalas@iitd.pan.wroc.pl
Anticancer Research
|August 27, 2011
Summary
Oncogenic Ras transformation up-regulates Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3), enhancing cancer cell sensitivity to cluster of differentiation 47 (CD47)-mediated cell death.
Area of Science:
- Cellular biology
- Cancer research
- Molecular oncology
Background:
- Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3) regulates cell death and autophagy.
- BNIP3 is implicated in cluster of differentiation 47 (CD47)-induced cell death.
- The effect of oncogenic transformation on BNIP3 expression is not well understood.
Purpose of the Study:
- To investigate the influence of oncogenic transformation on BNIP3 expression.
- To determine the role of BNIP3 in CD47-mediated cell death.
Main Methods:
- Utilized H-ras-transformed cells to study oncogenic transformation's effect on BNIP3 expression.
- Assessed sensitivity to CD47-mediated cell death using tetrazolium salt-based assays.
Main Results:
- Enforced and endogenous Ras expression correlated with BNIP3 up-regulation in various cancer cells.
- BNIP3 is a regulatory target of H-Ras, with oncogene introduction up-regulating BNIP3.
- CD47 ligation's effects were dependent on BNIP3 presence and Ras expression.
- Ras-transformed cells showed selective sensitivity to CD47-mediated cell death.
Conclusions:
- Oncogenic Ras directly influences BNIP3 expression.
- BNIP3 mediates selective sensitivity of Ras-transformed cells to CD47-induced death.
- BNIP3 plays a crucial role in Ras-driven cancer cell death pathways.
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:
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...
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...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...