BEX1 (brain expressed, X-linked 1)

2012-01-01   Biaoyang Lin , Jing Zhang , Greg Foltz 

Swedish Medical Center, Seattle, WA, USA (BL, GF); Zhejiang-California International NanoSystems Institute, Zhejiang Univ Hangzhou, China (BL, JZ)

Identity

HGNC
LOCATION
Xq22.1
LOCUSID
ALIAS
BEX2,HBEX2,HGR74-h

DNA/RNA

Note

There was some confusion in the nomenclature of the human BEX genes. The BEX1 referred in the publications (Quentmeier et al., 2005; Yang et al., 2002) is actually BEX2. BEX2, represented by the Genbank accession number AF220189, was called BEX1 by Yang et al. and others (Quentmeier et al., 2005; Yang et al., 2002). Later on, Alvarez et al. found that AF220189 is more similar to mouse Bex2 than to mouse Bex1 (74% and 68% identical, respectively) and that its chromosomal localization matches that of mouse Bex2 (Alvarez et al., 2005). Therefore, AF220189 is considered the human homologue of mouse Bex2, and is human BEX2.
Atlas Image
A diagram using the UCSC genome browser showing the locations of the five BEX members in the order of BEX5-BEX1-BEX4-BEX2-NGFRAP1 (nerve growth factor receptor (TNFRSF16) associated protein 1, BEX3) on the X chromosome at Xq22.1-2, along with other genes in the region.

Description

BEX1 encodes a gene belonging to the brain expressed X-linked gene family. It is a putative tumor suppressor as it is silenced in human glioma (Foltz et al., 2006). The BEX1 gene contains three exons, but the coding region is contained in one single exon.

Proteins

Note

Interacts with neurotrophin receptor p75NTR/NGFR (Naderi et al., 2007). Interacts with olfactory marker protein (OMP) (Koo et al., 2004).

Description

The BEX1 protein (NP_060946.3) has 125 amino acid residues.

Expression

Koo et al. assessed the expression pattern of Bex proteins in several different mouse tissues by western blot analysis (Koo et al., 2004). They used a polyclonal chicken antibody directed against a peptide common to the C-terminal region of mouse Bex1 and -2, which are 87% identical and 90% similar in amino acid sequences. They found that Bex1 and -2 proteins are expressed in mouse whole brain without olfactory bulb, olfactory bulb, olfactory epithelium and at a lower level in the heart, kidney, and liver but, not in the lung (Koo et al., 2004).

Localisation

Nucleus and cytoplasm (Koo et al., 2004).

Function

BEX1 plays a role in cell cycle progression as Bex1 levels oscillated during the cell cycle (Vilar et al., 2006). BEX1 also participates in neuronal differentiation (Vilar et al., 2006). Nerve growth factor (NGF) is a member of the neurotrophin family proteins that mediate survival, growth and differentiation of neuronal and glial cells by binding to two different types of cell surface receptors, the Trk tyrosine kinases - TrkA, TrkB and TrkC - and the p75 neurotrophin receptor (p75NTR). Vilar et al. showed that Bex1 competed with RIP2 (receptor-interacting serine-threonine kinase 2) for binding to the p75NTR intracellular domain, and elevating RIP2 levels restored the ability of cells overexpressing Bex1 to differentiate in response to NGF (Vilar et al., 2006). They further demonstrated that, in PC12 cells, Bex1 overexpression inhibited the induction of NF-kappaB activity by NGF without affecting activation of Erk1/Erk2 and AKT, while Bex1 knockdown accelerated neuronal differentiation and potentiated NF-kappaB activity in response to NGF (Vilar et al., 2006).

Homology

Five BEX members have been identified in human. They are BEX1, BEX2, NGFRAP1 (nerve growth factor receptor (TNFRSF16) associated protein 1, BEX3), BEX4, and BEX5. They are all clustered on the X chromosome at Xq22.1-2 (Alvarez et al., 2005).

Mutations

Note

None identified.

Implicated in

Entity name
Glioma
Note
We showed that BEX1 and BEX2 are candidate tumor suppressor genes in malignant glioma in a genome-wide analysis of epigenetic silencing in gliomas (Foltz et al., 2006). We found that BEX1 and BEX2 were reactivated by trichostatin A (TSA), a histone deacetylase inhibitor, or 5-aza-2-deoxycytidine (5-AzaC), a DNA methyltransferase inhibitor in glioma cell line T98 and U87, and 10 patient-derived primary glioma cell lines (Foltz et al., 2006). We demonstrated that BEX1 and BEX2s expression were silenced in GBM specimens because of extensive promoter hypermethylation at their promoters. Re-expression of either BEX1 or BEX2 led to increased sensitivity to chemotherapy-induced apoptosis and potent tumor suppressor effects in vitro and in a xenograft mouse model (Foltz et al., 2006). We further showed that BEX1 and BEX2 in GBM cells were down regulated by SOX2, a key gene implicated in maintaining the stemness of embryonic and adult stem cells (Fang et al., 2011).
Disease
Gliomas are the primary cancers derived from glial cells in the brain. It is the most frequent cerebral neoplasias. Astrocytomas are the most common type of gliomas. They are slow-growing, and can be found anywhere in the brain, but most often found in the cerebrum. They can be clinically divided into four grades, with glioblastoma (World Health Organization grade IV) being the most common and aggressive.

Bibliography

Pubmed IDLast YearTitleAuthors
159582832005Characterization of the Bex gene family in humans, mice, and rats.Alvarez E et al
212110352011The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis.Fang X et al
168186402006Genome-wide analysis of epigenetic silencing identifies BEX1 and BEX2 as candidate tumor suppressor genes in malignant glioma.Foltz G et al
151986712004The interaction of Bex and OMP reveals a dimer of OMP with a short half-life.Koo JH et al
176388832007BEX2 is overexpressed in a subset of primary breast cancers and mediates nerve growth factor/nuclear factor-kappaB inhibition of apoptosis in breast cancer cell lines.Naderi A et al
159204852005Expression of BEX1 in acute myeloid leukemia with MLL rearrangements.Quentmeier H et al
164984022006Bex1, a novel interactor of the p75 neurotrophin receptor, links neurotrophin signaling to the cell cycle.Vilar M et al
119897832002Cloning and expression pattern of a spermatogenesis-related gene, BEX1, mapped to chromosome Xq22.Yang QS et al

Other Information

Locus ID:

NCBI: 55859
MIM: 300690
HGNC: 1036
Ensembl: ENSG00000133169

Variants:

dbSNP: 55859
ClinVar: 55859
TCGA: ENSG00000133169
COSMIC: BEX1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000133169ENST00000372728Q9HBH7

Expression (GTEx)

0
100
200
300
400
500
600
700

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
168186402006Genome-wide analysis of epigenetic silencing identifies BEX1 and BEX2 as candidate tumor suppressor genes in malignant glioma.50
233621082013Epigenetic regulation of the X-linked tumour suppressors BEX1 and LDOC1 in oral squamous cell carcinoma.25
256122942015Brain expressed and X-linked (Bex) proteins are intrinsically disordered proteins (IDPs) and form new signaling hubs.11
190287012009Inhibition of apoptosis by downregulation of hBex1, a novel mechanism, contributes to the chemoresistance of Bcr/Abl+ leukemic cells.10
246262992014BEX1 promotes imatinib-induced apoptosis by binding to and antagonizing BCL-2.10
260466702015BEX1 acts as a tumor suppressor in acute myeloid leukemia.9
243337342014Epigenetic genome-wide analysis identifies BEX1 as a candidate tumour suppressor gene in paediatric intracranial ependymoma.8
119897832002Cloning and expression pattern of a spermatogenesis-related gene, BEX1, mapped to chromosome Xq22.7
291921392017BEX1 is an RNA-dependent mediator of cardiomyopathy.5
301325322018Low expression of BEX1 predicts poor prognosis in patients with esophageal squamous cell cancer.1

Citation

Biaoyang Lin ; Jing Zhang ; Greg Foltz

BEX1 (brain expressed, X-linked 1)

Atlas Genet Cytogenet Oncol Haematol. 2012-01-01

Online version: http://atlasgeneticsoncology.org/gene/44161/bex1