ASXL1 is one of the most frequently mutated genes in myeloid malignancies and is associated with poor clinical outcomes. The molecular mechanisms by which ASXL1 gene mutations drive the development of these diseases are still under investigation. Armed with rich experience in biomarker analysis and diverse technique platforms, Creative Biolabs provides one-stop ASXL1 analysis services for global clients.
ASXL1 Structure and Mutations
ASXL1 gene is known to mutate in a variety of myeloid hematologic tumors. The mutation of ASXL1 gene almost occurred in exon 12, accounting for more than 95% of all mutations. The mutations of ASXL1 mostly co-occur with the mutations of other genes and have synergistic effects.
Fig.1 Patterns of ASXL1 genetic alterations.1
ASXL1 Protein Complex in Tumors
Normally, ASXL1 and BAP1 protein complex, binds to transcription factors FOXK1/K2 that recognize specific DNA sequences, and is recruited to a specific region of the genome, reduces the level of histone H2AK119ub1 in that region, transcribs and activates downstream target genes.
Fig.2 Working model of the ASXL1 protein complex.1, 2
In hematologic tumors, the C-truncated ASXL1 mutant protein still binds to BAP1 but completely loses its ability to bind to FOXK1 and FOXK2, leading to the dominant negative effect of ASXL1 mutation. Moreover, the transcriptional regulation function of ASXL1 complex was significantly weakened, and the expression of a series of tumor suppressor genes was down-regulated, thus regulating glucose metabolism, hypoxia perception, tumor-related signaling pathways.
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Studies have shown that ASXL1 plays a decisive role in maintaining the homology of genes and the stability of expression of different gene loci. And ASXL1 mutations are associated with the pathogenesis of a variety of diseases. The follow is some of the relevant studies:
Neurocognitive deficiencies
There is a marked increase in neurological abnormalities in patients with ASLD.
Hepatic disease
Liver involvement in patients with ASLD ranges from hepatomegaly to elevated liver enzymes to severe liver fibrosis.
Hypertension
Hypertension is overrepresented in patients with ASLD, and secondary causes of hypertension are often not detected.
Electrolyte imbalances
Some patients with ASLD may develop electrolyte imbalances, such as hypokalemia, of unknown etiology.
A
ASXL1 deficiency can lead to bone hypoplasia and bone defects.
B
ASXL1 mutations are associated with hematopoietic progenitor cell proliferation in primary bone marrow cells.
C
ASXL1 is a tumor suppressor gene that is required to activate INK4B in response to carcinogenic and anti-proliferative signals.
D
The binding ability to functional protein BRD4 affects the level of histone acetylation, resulting in increased sensitivity of ASXL1 mutant cells to BET inhibitors.
E
The mutant protein of C-truncated ASXL1 can enhance the deubiquitination activity of BAP1 and affect the differentiation of myeloid hematopoietic cells.
These studies demonstrate the importance of ASXL1 for disease research. Our services can be customized to suit the specific needs of our clients, popular analysis services targeting ASXL1 include but are not limited to the following:
| Cat | Service |
|---|---|
| BAS115-1 | ASXL1 Antibody Development |
| BAS115-2 | ASXL1 Cell Proliferation/Apoptosis Assay |
| BAS115-3 | ASXL1 Protein Expression |
| BAS115-4 | ASXL1 Mutants Analysis |
| BAS115-5 | ASXL1 Gene Analysis |
| BAS115-6 | ASXL1 Protein Complex Analysis |
| BAS115-7 | ASXL1 Sequence Assay |
| BAS115-8 | ASXL1 Immunofluorescence Assay |
| BAS115-9 | ASXL1 Immunoprecipitation Assay |
We are committed to providing the highest quality of custom services and products at the most reasonable prices. Please feel free to contact us for more information and a formal quote.
References
- Gelsi-Boyer, Véronique, et al. "Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases." Journal of hematology & oncology 5 (2012): 1-6.
- Xia, Yu-Kun, et al. "Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network." Protein & cell 12.7 (2021): 557-577. Distributed under CC BY-SA 4.0, without modification.
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