Related Experiment Videos
The oncoprotein gankyrin interacts with RelA and suppresses NF-kappaB activity
Hiroaki Higashitsuji1, Hisako Higashitsuji, Yu Liu
1Department of Clinical Molecular Biology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan. hhigashi@virus.kyoto-u.ac.jp
Biochemical and Biophysical Research Communications
|October 2, 2007
Summary
Gankyrin, an oncoprotein, directly binds to NF-kappaB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) and suppresses its transcriptional activity. This interaction involves modulating acetylation through SIRT1, impacting hepatocellular carcinoma progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gankyrin is an oncoprotein overexpressed in hepatocellular carcinoma.
- It interacts with proteins and degrades tumor suppressors like Rb and p53.
- Gankyrin's ankyrin repeats suggest structural similarity to IkappaBs, hinting at NF-kappaB pathway involvement.
Purpose of the Study:
- To investigate the interaction between gankyrin and NF-kappaB.
- To elucidate the mechanism by which gankyrin affects NF-kappaB transcriptional activity.
Main Methods:
- Co-immunoprecipitation to confirm gankyrin-RelA binding.
- Reporter assays to measure NF-kappaB transcriptional activity in response to gankyrin overexpression/down-regulation.
- Treatment with TNFalpha, Leptomycin B, nicotinamide, and SIRT1 inhibitors/knockdown.
Main Results:
- Gankyrin directly binds to the RelA subunit of NF-kappaB.
- Gankyrin overexpression suppresses basal and TNFalpha-induced NF-kappaB activity.
- Gankyrin's inhibitory effect is mediated at the transcriptional level, independent of RelA DNA binding or nuclear translocation, and involves SIRT1-dependent acetylation.
Conclusions:
- Gankyrin directly interacts with NF-kappaB and inhibits its transcriptional activity.
- The mechanism involves modulation of NF-kappaB acetylation via SIRT1.
- Gankyrin represents a potential therapeutic target in hepatocellular carcinoma by interfering with the NF-kappaB pathway.
Related Concept Videos
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
02:04Co-activators and Co-repressors
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
01:00Enzyme-linked Receptors
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
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,...
02:26NF-kB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
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...