Abstract

The brain and acute leukemia cytoplasmic (BAALC; UniProt entry Q8WXS3) is a 180-residue-long human protein having six known isoforms. BAALC is expressed in either hematopoietic or neuroectodermal cells and its specific function is still to be revealed. However, as a presumably membrane-anchored protein at the cytoplasmic side it is speculated that BAALC exerts its function at the postsynaptic densities of certain neurons and might play a role in developing cytogenetically normal acute myeloid leukemia (CN-AML) when it is highly overexpressed by myeloid or lymphoid progenitor cells. In order to better understand the physiological role of BAALC and to provide the basis for a further molecular characterization of BAALC, we report here the 1H, 13C, and 15N resonance assignments for the backbone nuclei of its longest hematopoietic isoform (isoform 1). In addition, we present a 1HN and 15NH chemical shift comparison of BAALC with its shortest, neuroectodermal isoform (isoform 6) which shows only minor changes in the 1H and 15N chemical shifts.

Highlights

  • The brain and acute leukemia cytoplasmic (BAALC; UniProt entry Q8WXS3) is a human protein of 180 amino acids

  • Its over-expression is strongly correlated in cytogenetically normal acute myeloid leukemia (CN-AML) (Weber et al 2014; Zhou et al 2015), that is more prevalent with progressing age, and associates with poor outcome questioning the correlation as a pure coincidence

  • Understanding the signalling leading to myeloid progenitor cell proliferation and differentiation is indispensable to obtain a deeper understanding of leukemogenesis

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Summary

Biological context

The brain and acute leukemia cytoplasmic (BAALC; UniProt entry Q8WXS3) is a human protein of 180 amino acids. The remaining three splice variants encode the same predicted 80-amino-acid protein (isoform 4). These isoforms are expressed in cells of hematopoietic or neuroectodermal origin. The BAALC gene was shown to be expressed mainly in hematopoietic progenitor cells and to be down-regulated during their differentiation (Baldus et al 2003a). RUNX1 is a transcription factor important for hematopoietic cell development during embryogenesis (Tober et al 2016) and as a hybrid protein formed by fusions of AML1 and ETO, a genetic aberration leading to the acute myeloid leukemia subtype M2 (Lin et al 2017). This study presents 1H, 15N and 13C backbone resonance assignments to provide the basis for an atom-based structural view on the BAALC protein and its interactions employing high-resolution NMR spectroscopy

Protein expression and purification
NMR spectroscopy
Structure prediction
Findings
Extent of assignments and data deposition
Full Text
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