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- Table of Contents
Facts about E3 ubiquitin-protein ligase TRIP12.
In normal cells, mediates ubiquitination and degradation of isoform p19ARF/ARF of CDKN2A, a lysine-less tumor suppressor needed for p53/TP53 activation under oncogenic stress. In cancer cells, however, isoform p19ARF/ARF and TRIP12 are located in different cell compartments, preventing isoform p19ARF/ARF ubiquitination and degradation.
Human | |
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Gene Name: | TRIP12 |
Uniprot: | Q14669 |
Entrez: | 9320 |
Belongs to: |
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UPL family |
EC 6.3.2.-; KIAA0045ULF; MGC138849; MGC138850; probable E3 ubiquitin-protein ligase TRIP12; thyroid hormone receptor interactor 12; thyroid receptor interacting protein 12; Thyroid receptor-interacting protein 12; TR-interacting protein 12; TRIP-12
Mass (kDA):
220.434 kDA
Human | |
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Location: | 2q36.3 |
Sequence: | 2; NC_000002.12 (229763837..229923234, complement) |
Nucleus, nucleoplasm.
If you've been wondering how to use the TRIP12 marker, here's some information for you. TRIP12 contributes towards cell death via mediating ubiquitination. You can also learn more about the other uses this marker has in this article. I hope you find this information useful. If not, I'll share a few of the best uses for this marker.
Additional sexcombs-1, a member of the ASXL family is an important one. Its role within epigenetic regulation is not fully understood. However, patients with myeloid-related neoplasms have been found to have C-terminally trincated mutant forms of this protein. Mutations in this gene have been linked to poorer prognosis.
The ASXL1 subunit is responsible for ubiquitination. The ASXL1-MT protein is ubiquitinated by the ubiquitin ligase BAP1 (ubiquitin-polymerase I). BAP1 recruits ubiquitin and stabilizes them, thereby promoting ubiquitination.
Mutations of ASXL1 lead to loss of transcriptional repression in hematopoietic cells and leukemogenic target gene expression. The Drosophila PR–DUB complex's molecule structure shows that ASXL1, Calypso and Calypso have a complex that blocks H2AK119Ub deubiquitinating. Mutations in ASXL1 have been linked to cancer and other diseases.
Mutations in ASXL1 were more stable than wild type ASXL1 protein. ASXL1 mutations led to higher cell viability and proliferation in K562 cells under serum-deprivation conditions. The C-terminal truncated mutant ASXL1 protein promoted cell proliferation and inhibited apoptosis.
The study also revealed that ASXL1-MT promotes the recruitment of BAP1 to chromatin, whereas it does not affect H2AK119ub. ASXL1 -MT is also upregulated by cells with defective Bap1.
ASXL1 interacts with a number of other proteins, including the transcriptional factor BAP1 and the polycomb repressive complex (PR-DUB) protein. ASXL1 mediates the ubiquitination of plant homeodomain finger (PR-DUB) and BAP1, which are components of the PR–DUB complex. ASXL1 mediates the ubiquitination of mammalian cells through the polycomb regulatory complex.
ASXL1 mutations cause premature sister-chromatid separation. A loss of cohesin-proteins can also cause premature sister chromatid division. Loss in AsxL1 causes chromatin to become stale at telophase. Additional human primary cell studies are needed to validate the findings. Asxl1 is involved with maintaining normal sister chromatid seperation.
Cell growth can be disrupted by AsxL1 mutations. ASXL1 mutations inhibit the self-renewal mesenchymalstromal cells and inhibit the differentiation of erythropoiesis. It alters gene expression of genes implicated in apoptosis. It also promotes survival in apoptotic cancer cells. It does not confer self-renewal on HSPCs.
In vitro studies have shown that ASXL1 interacts to the FOXK1 proteins. ASXL1N646Flag, however, forms a weak connection with FOXK1/K2 in human cells. Mutant ASXL1C-terminal transtroncation proteins maintain a functional interaction to FOXK1/K1/2. These mutants do not promote gene transcription through mono-ubiquitination of H2AK119.
ASXL1 in the human cell is essential for normal separation of chromatids and allows gene expression. It is involved in the interaction with cohesin complex proteins and regulates transcription. Normal gene expression is dependent on the interaction between ASXL1 proteins and cohesin, which prevents dysplastic forms. The molecular mechanism through which ASXL1 mediates and inhibits ubiquitination is still not fully understood.
The TRIP12 protein is a member of the N-degron pathway, a ubiquitin-dependent proteolytic pathway that regulates protein half-life by recognizing degradation signals from their N-terminal ends. It is composed of two proteins, Ubc13, and Ubc21. This protein interacts with the cognate E3s to regulate degradation of other protein. In yeast, these two proteins interact to increase substrate ubiquitination.
TRIP12 serves as an E3 within the UFD pathway. It can ubiquitinate UBB+1. This is a component the apoptotic signals pathway. UBB+1, a target of this pathway is knockdown of TRIP12 reduces the viability of cells by half. TRIP12 is involved with the UBB+1-induced cell deaths.
TRIP12 proteins have multiple biological functions. They regulate nine different substrates of proteolysis. This makes it a promising therapeutic candidate. However, there are several questions that remain about the exact mechanism in which TRIP12 regulates cell death. TRIP12, like other proteins, requires further research to determine its role in controlling cell cycle progression as well as maintaining genome integrity. For now, however it seems that TRIP12 can be used for cell death research.
TRIP12 is a member the HECT E3 family of ubiquitin-ligase proteins. It was first detected in mice. It was also characterized for embryonic lethality. Its function in cell death has since been characterized in a number of cancers and is a predictive marker for therapeutic responses. It is therefore an important tool in detecting cell death. This discovery could have implications for cancer research.
TRIP12 may also play a part in the UFD pathway. Human cells with the TRIP12 gene can efficiently degrade the UFD substrates in vitro. They may also direct ubiquitination of UFD substrates in vivo. The TRIP12 HECT Domain may also contain a non-covalent binding site for ubiquitin, making it a good candidate for the UFD path.
After transfection, HeLa cells were exposed to lentivirus-containing supernatant for 16 hours. Hoechst33258 (20ng/ml) was used for a fluorescent indicator for two minutes. After the exposure, samples were collected and the GFP signal was detected by Western blotting using an anti-GFP antibody. All experiments were carried out at least 3 times.
PMID: 20208519 by Chen D., et al. Transcription-independent ARF regulation in oncogenic stress-mediated p53 responses.
PMID: 7776974 by Lee J.W., et al. Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor.