ASXL2 Antibody (Rabbit mAb) [P15A4] Datasheet

Biological Description

Specificity	ASXL2 Antibody (Rabbit mAb) [P15A4] detects endogenous levels of total ASXL2 protein.
Background	ASXL2 (additional sex combs-like 2) is a chromatin regulator of the ASXL family. Its best-known partner is the tumour-suppressor deubiquitinase BAP1, which forms the core of a histone H2A deubiquitinase complex. BAP1 forms two separate complexes, one with ASXL1 and one with ASXL2, never both together, and these partnerships help keep BAP1 protein levels steady. BAP1 is in turn needed to stabilise ASXL2 but not ASXL1, so ASXL2 becomes unstable and loses its function when BAP1 is lost in cancer. The ASXM domain of ASXL2 binds the C-terminal domain of BAP1. This contact is needed for BAP1 to bind ubiquitin and remove it from histone H2A at lysine 119. Contacts between the catalytic and non-catalytic regions of BAP1 form a composite ubiquitin-binding surface, with the catalytic domain gripping the hydrophobic patch of ubiquitin and the C-terminal domain holding its charged patch. Cancer-associated BAP1 mutations can disrupt this surface. An in-frame deletion in the C-terminal domain blocks ASXL binding, weakens deubiquitinase activity and deregulates proliferation, and ASXL2 mutations found in cancer also reduce BAP1 activity. The BAP1–ASXL2 interaction also helps control cellular senescence. ASXL2 is required for normal blood formation. Deleting Asxl2 in adult mouse bone marrow causes rapid falls in white blood cells and platelets, myelodysplasia-like changes in neutrophils, erythroid progenitors and megakaryocytes, and poor self-renewal of haematopoietic stem and progenitor cells. Losing just one allele is enough to impair self-renewal, so normal function depends on the full gene dose. ASXL2 and ASXL1 do not overlap in what they do: loss of ASXL2 disrupts a much larger, distinct set of genes, and these are mostly direct targets of RUNX1 and of the AML1-ETO fusion oncoprotein. ASXL2 is strongly enriched at AML1-ETO binding sites, and its loss raises H3K27ac and H3K4me1 at active and poised enhancers. It also reduces TET2 and NOTCH2 expression and opens chromatin at the HoxA and Meis1 loci. Truncating ASXL2 mutations are common in acute myeloid leukaemia with the t(8;21) translocation and produce an unstable protein. Asxl2 loss shortens the time to leukaemia in AML1-ETO mouse models and gives rise to a transcriptionally distinct subset of patient samples.

Specificity

ASXL2 Antibody (Rabbit mAb) [P15A4] detects endogenous levels of total ASXL2 protein.

Background

ASXL2 (additional sex combs-like 2) is a chromatin regulator of the ASXL family. Its best-known partner is the tumour-suppressor deubiquitinase BAP1, which forms the core of a histone H2A deubiquitinase complex. BAP1 forms two separate complexes, one with ASXL1 and one with ASXL2, never both together, and these partnerships help keep BAP1 protein levels steady. BAP1 is in turn needed to stabilise ASXL2 but not ASXL1, so ASXL2 becomes unstable and loses its function when BAP1 is lost in cancer. The ASXM domain of ASXL2 binds the C-terminal domain of BAP1. This contact is needed for BAP1 to bind ubiquitin and remove it from histone H2A at lysine 119. Contacts between the catalytic and non-catalytic regions of BAP1 form a composite ubiquitin-binding surface, with the catalytic domain gripping the hydrophobic patch of ubiquitin and the C-terminal domain holding its charged patch. Cancer-associated BAP1 mutations can disrupt this surface. An in-frame deletion in the C-terminal domain blocks ASXL binding, weakens deubiquitinase activity and deregulates proliferation, and ASXL2 mutations found in cancer also reduce BAP1 activity. The BAP1–ASXL2 interaction also helps control cellular senescence. ASXL2 is required for normal blood formation. Deleting Asxl2 in adult mouse bone marrow causes rapid falls in white blood cells and platelets, myelodysplasia-like changes in neutrophils, erythroid progenitors and megakaryocytes, and poor self-renewal of haematopoietic stem and progenitor cells. Losing just one allele is enough to impair self-renewal, so normal function depends on the full gene dose. ASXL2 and ASXL1 do not overlap in what they do: loss of ASXL2 disrupts a much larger, distinct set of genes, and these are mostly direct targets of RUNX1 and of the AML1-ETO fusion oncoprotein. ASXL2 is strongly enriched at AML1-ETO binding sites, and its loss raises H3K27ac and H3K4me1 at active and poised enhancers. It also reduces TET2 and NOTCH2 expression and opens chromatin at the HoxA and Meis1 loci. Truncating ASXL2 mutations are common in acute myeloid leukaemia with the t(8;21) translocation and produce an unstable protein. Asxl2 loss shortens the time to leukaemia in AML1-ETO mouse models and gives rise to a transcriptionally distinct subset of patient samples.

Usage Information

Application

WB

Dilution

WB

1:1000

Reactivity

Human, Monkey

Source

Rabbit Monoclonal Antibody

MW

154 kDa

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/26416890/
https://pubmed.ncbi.nlm.nih.gov/28516957/

ASXL2 Antibody (Rabbit mAb) [P15A4]

Biological Description

Usage Information

References

Application Data