RREB1 (Ras Responsive Element Binding Protein 1)

2014-02-01   Renty B Franklin , Leslie C Costello 

Department of Oncology, Diagnostic Sciences, Dental School, The Greenebaum Cancer Center, University of Maryland, Baltimore, MD, 21201, USA

Identity

HGNC
LOCATION
6p24.3
LOCUSID
ALIAS
FINB,HNT,LZ321,RREB-1,Zep-1
FUSION GENES

Abstract

Review on RREB1 (Ras Responsive Element Binding Protein 1), with data on DNA, on the protein encoded, and where the gene is implicated.

DNA/RNA

Description

The RREB1 gene is 144384 bp. The mRNA is 8568 bp and codes a protein of 1742 amino acids. Nine splice variants of RREB1 are predicted. Variant 1 contains 13 coding exons.

Transcription

Five isoforms of RREB1 designated RREB1 alpha, RREB1 beta, RREB1 delta, RREB1 gamma and RREB1 epsilon are expressed through alternative splicing.

Pseudogene

None reported.

Proteins

Atlas Image
Schematic diagram of Homo sapiens RREB1 protein showing clusters of conserved zinc figures (ZnF).

Description

RREB1 is a zinc finger nuclear protein of 1742 amino acids that contains 15 zinc fingers of the C2H2 type and belongs to the Krueppel zinc-finger protein family. RREB1 protein-protein interactions include NEUROD1 (Ray et al., 2003) and AR (Mukhopadhyay et al., 2007).

Expression

RREB1 is ubiquitously expressed in most tissues; however, it may not be expressed in brain.

Localisation

RREB1 expression is localized to nucleus speckle (Date et al., 2004; Fujimoto-Nishiyama et al., 1997).

Function

RREB1 binds specifically to the ras-responsive element (RRE) of genes to activate promoter activity and gene transcription. It is involved in regulation of calcitonin expression (Thiagalingam et al., 1996). RREB1 is reported to both activate and repress transcription (Chen et al., 2010). RREB1 reportedly negatively regulates the transcriptional activity of the androgen receptor (Mukhopadhyay et al., 2007). RREB1 is reported to play a role in cell to cell adhesion and regulation of cell movement (Melani et al., 2008). The specific roles of the individual spliced forms are not well defined. RREB1 alpha is not required for proliferation of bladder cancer lines; however, RREB1 beta may be required (Nitz et al., 2011).

Homology

With members of the Krueppel family of zinc finger proteins.

Mutations

Note

No disease related mutations are reported.

Implicated in

Entity name
Colorectal cancer
Note
RREB1 is implicated in Ras signaling pathways.
RREB1 is activated through phosphorylation by the MAPK pathway in colorectal cancer (Kent et al., 2013). RREB may play an important role in the development of the primitive gut tube (Lee et al., 2012).
Entity name
Prostate adenocarcinoma.
Note
RREB1 represses the expression of ZIP1 zinc transporter in prostate epithelial cells. Up-regulation of RREB1 in prostate cancer may lead to loss of ZIP1 expression, zinc accumulation and progression of prostate cancer (Milon et al., 2010; Zou et al., 2011).
Atlas Image
RREB1 expression in normal and prostate cancer tissue sections.
Entity name
Pancreatic cancer
Note
The zinc level are markedly decreased in pancreatic cancer. The loss of zinc removes its cytotoxic effects on malignant cells. The change in zinc level is associated with decreased expression of the ZIP3 zinc transporter. Recent studies demonstrate that ZIP3 and RREB1 are markedly down regulated with cellular zinc levels. In addition, these changes in zinc, ZIP3 and RREB1 are apparent in PanIn lesions, which are thought to be precancerous lesions leading to ductal adenocarcinoma. Results suggest that down regulation of RREB1 causes down regulation of ZIP3, which results in loss of zinc accumulation in premalignant pancreatic ductal cells (Costello et al., 2012).

Bibliography

Pubmed IDLast YearTitleAuthors
201339352010Developmental silencing of human zeta-globin gene expression is mediated by the transcriptional repressor RREB1.Chen RL et al
224271552012Evidence for changes in RREB-1, ZIP3, and Zinc in the early development of pancreatic adenocarcinoma.Costello LC et al
150673622004Finb, a multiple zinc finger protein, represses transcription of the human angiotensinogen gene.Date S et al
93057721997A novel zinc finger protein, Finb, is a transcriptional activator and localized in nuclear bodies.Fujimoto-Nishiyama A et al
211598162010Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway.Kent OA et al
217920862012Proteomic identification of RREB1, PDE6B, and CD209 up-regulated in primitive gut tube differentiated from human embryonic stem cells.Lee DH et al
183948912008Regulation of cell adhesion and collective cell migration by hindsight and its human homolog RREB1.Melani M et al
198028702010Ras responsive element binding protein-1 (RREB-1) down-regulates hZIP1 expression in prostate cancer cells.Milon BC et al
175509812007The zinc finger protein ras-responsive element binding protein-1 is a coregulator of the androgen receptor: implications for the role of the Ras pathway in enhancing androgenic signaling in prostate cancer.Mukhopadhyay NK et al
217034252011RREB1 transcription factor splice variants in urologic cancer.Nitz MD et al
174969272007Expression profiling of Ral-depleted bladder cancer cells identifies RREB-1 as a novel transcriptional Ral effector.Oxford G et al
124829792003Novel transcriptional potentiation of BETA2/NeuroD on the secretin gene promoter by the DNA-binding protein Finb/RREB-1.Ray SK et al
88164451996RREB-1, a novel zinc finger protein, is involved in the differentiation response to Ras in human medullary thyroid carcinomas.Thiagalingam A et al
213605632011hZIP1 zinc transporter down-regulation in prostate cancer involves the overexpression of ras responsive element binding protein-1 (RREB-1).Zou J et al

Other Information

Locus ID:

NCBI: 6239
MIM: 602209
HGNC: 10449
Ensembl: ENSG00000124782

Variants:

dbSNP: 6239
ClinVar: 6239
TCGA: ENSG00000124782
COSMIC: RREB1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000124782ENST00000334984Q92766
ENSG00000124782ENST00000349384Q92766
ENSG00000124782ENST00000349384A0A024QZU8
ENSG00000124782ENST00000379933Q92766
ENSG00000124782ENST00000379933A0A024QZU8
ENSG00000124782ENST00000379938Q92766
ENSG00000124782ENST00000471433C9JPJ6
ENSG00000124782ENST00000483150C9JU34
ENSG00000124782ENST00000491191C9JE09
ENSG00000124782ENST00000611109A0A087X055

Expression (GTEx)

0
5
10
15
20
25
30
35
40

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
208848462010Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors.135
211598162010Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway.132
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
227511222013RREB1 repressed miR-143/145 modulates KRAS signaling through downregulation of multiple targets.56
127006642003p16 INK4a gene promoter variation and differential binding of a repressor, the ras-responsive zinc-finger transcription factor, RREB.34
183948912008Regulation of cell adhesion and collective cell migration by hindsight and its human homolog RREB1.30
198900572009RREB-1 is a transcriptional repressor of HLA-G.28
216138272011Decreased zinc and downregulation of ZIP3 zinc uptake transporter in the development of pancreatic adenocarcinoma.24
266087852015Histone Modifier Genes Alter Conotruncal Heart Phenotypes in 22q11.2 Deletion Syndrome.21
195583682009DNA damage signalling recruits RREB-1 to the p53 tumour suppressor promoter.17

Citation

Renty B Franklin ; Leslie C Costello

RREB1 (Ras Responsive Element Binding Protein 1)

Atlas Genet Cytogenet Oncol Haematol. 2014-02-01

Online version: http://atlasgeneticsoncology.org/gene/51424/rreb1