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POU4F1 (POU class 4 homeobox 1)

Identity

Other namesBRN3A
Brn-3a
FLJ13449
Oct-T1
RDC-1
Hugo POU4F1
Location 13q31.1
Local_order Gene orientation: minus strand
Note Member of class IV POU domain transcription factor.

DNA/RNA

Description The gene is about 4,468 bases encoded by two exons separated by a short intron.
Transcription 5', upstream promoter drives expression of longer Brn-3a transcript encoding for Brn-3a(l) protein which includes exons 1 and 2. Regulatory sequences within the intron control expression of short Brn-3a transcript entirely from exon 2, which encodes Brn-3a(s) protein.

Protein

 
  Schematic diagram showing the two isoforms of Brn3-a protein that can be derived from the Brn-3a gene as a result of alternative promoter usage (P1 and P2). AD refers to N-terminal activation domain present only in Brn-3a(l). POU domain found at the C' terminal of the protein is common to both Brn-3a(l) and Brn-3a(s).
Description Protein product for Brn-3a(l) is 423 amino acids with estimated molecular weight of about 42.9 kDa whereas Brn-3a(s) protein is 339 amino acids; about 32 kDa.
Expression Nervous System: Originally isolated from brain cDNA, Brn-3a is expressed in specific neurons of midbrain and hindbrain in CNS and in peripheral sensory neurons (trigeminal ganglia, dorsal root ganglia, spinal cord). It is first seen in neural crest cells that are destined to form sensory neurons and expression persists in mature neurones. Brn-3a is also expressed in retinal ganglion cells and vestibular somatosensory cells, where it cooperates with Brn-3b and Brn-3c respectively to determine cell fate.
Non-neuronal cell: Brn-3a is also expressed in T-cells, heart, testis, ovary, breast epithelium.
Cancers: implicated in neuroblastoma, Ewing sarcoma, cervical cancers, prostate cancers.
Localisation Nuclear
Function Brn-3a proteins act as transcription factors to regulate the expression of target genes, which can alter cell fate. In neuron, Brn-3a protects cells from apoptosis (by transactivating anti-apoptotic genes while repressing expression of pro-apoptotic proteins -see below). Brn-3a also enhances differentiation of neuronal cells in vitro and in-vivo by its ability to transactivate multiple neuronal target promoters. Brn-3a is required for the generation of proprioceptors in trigeminal ganglia.
The POU domain found at the C' terminal end of Brn-3a proteins is a bipartite DNA binding domain that can recognize and bind with high affinity and specificity to specific DNA sequences present in the promoters of target genes. DNA consensus sites recognized by Brn-3a include a core A/T rich octamer sequence e.g. ATAATTAAT with the POU-homeodomain (POU-HD) facilitating high affinity binding, whilst the POU-specific (POU-s) domain enhances specificity.
The POU domain of Brn-3a protein also has transactivation function and since Brn-3a(l) and Brn-3a(s) are identical in this region, both proteins can regulate specific subsets of target genes that require POU domain transactivation function e.g. neurofilament, SNAP 25, synaptophysin, Hsp-27. However, some Brn-3a target genes require the N' terminal transactivation domain that is found only in Brn-3a(l) protein and therefore these target genes can only be activated by Brn-3a(l) protein e.g. Bcl-2, Bcl-XL, alpha-internexin. Other target genes regulated by Brn-3a include TrkA, neuroD1 and neuroD4, Nav1.7 sodium channel, Doppel glycoprotein, iNOS, p53, NGFI-A, Hsp-27, tyrosine hydroxylase. Brn-3a also auto-regulate its own expression.
In addition to its direct effects on specific target genes, Brn-3a can also alter gene expression by its interaction with other cellular factors. For example, Brn-3a interacts physically with p53 protein, and modifies its effects on specific target genes that regulate cell fate. Thus Brn-3a cooperates with p53 to increase the expression of the cell cycle regulator, p21cip1/waf1 whilst antagonising p53 mediated expression of pro-apoptotic target genes, Bax and Noxa.
Brn-3a other interacting partner includes Rin1 (on target gene, Egr1), HIPK1 (alters TrkA expression), EWS- Fli1 fusion protein (represses Brn-3a mediated effects on survival / differentiation genes).
In addition to cellular target genes, Brn-3a also controls expression of viral genes such as those encoding the human papilloma virus (HPV) immediate early E6/E7 gene (required for HPV transformation of cervical cells) by binding to and transactivating the viral promoter. It is thought that the ability of Brn-3a to transactivate this promoter contributes to its effects in transformation of cervical cancer cells.
Homology High homology with other POU4 family members in the POU domain (C' terminal end of the protein), and in the POU4 box (region of homology within the N' terminal transactivation domain, present only in Brn-3a(l)). Family members include mammalian POU4f2 (Brn-3b), POU4f3 (Brn-3c), drosophila I-POU and nematode, unc-86.

Implicated in

Entity Normal development of sensory neurons in CNS and PNS
Note Loss of Brn-3a by homologous recombination in mice resulted in significant loss of sensory neurons (e.g. in the midbrain, trigeminal ganglia, dorsal root ganglia) during development. Mutants die within the first day of birth. Studies using cultured neural crest cells demonstrate that Brn-3a expressing cells are destined for sensory lineage. Brn-3a is required for the survival of these cells and achieves this partly by inhibiting expression of p53 mediated, pro-apoptotic target genes. Neural crest cells cultured from Brn-3a knockout mice, undergo significant apoptosis as a result of increased expression of p53 pro-apoptotic target genes, bax and Noxa.
  
Entity Neuroblastomas
Oncogenesis Brn-3a mRNA is significantly reduced in neuroblastoma tumour biopsies. Studies undertaken using neuroblastoma cell lines showed that Brn-3a is expressed at low levels when the cells are actively proliferating. However, when cells are induced to cease dividing and undergo differentiation, Brn-3a is significantly increased in cells. Forced over-expression of Brn-3a protects cells from apoptosis but also induces differentiation and neurite outgrowth. Therefore, the significant decrease of Brn-3 in neuroblastoma tumours may contribute to the oncogenic changes in the cells.
  
Entity Neuroendocrine tumours
Oncogenesis Brn-3a was shown to be elevated in highly aggressive neuroendocrine tumours SCCL tumours and ACTH producing pituitary tumours.
  
Entity Ewing sarcoma
Oncogenesis Brn-3a was detected in some Ewing sarcomas, which are tumours derived from primitive neural ectodermal lineage. These tumours are characterised by rearrangement of genes encoding the Ewing sarcoma (EWS) protein, and members of the Ets family of transcription factors. The most common fusion protein, EWS/Fli1, produces cellular transformation. Brn-3a interacts with the EWS/Fli1 fusion protein, and this interaction prevents Brn-3a mediated transactivation of genes required for cell cycle arrest e.g. p21cip1/waf1 and neurite outgrowth e.g. SNAP-25.
  
Entity Cervical cancer
Oncogenesis Brn-3a is expressed at high levels in high-grade cervical intra-epithelial neoplasia (CIN 3) compared to normal cervical biopsies. In this context, Brn-3a may contribute to tissue formation by binding to regulatory regions of Human Papilloma Viruses, HPV-16 and HPV18 and regulate expression of their oncogenic E6 and E7 genes.
  
Entity Prostate cancer
Oncogenesis Brn-3a was also detected in prostate cancers with up to 50% of tumours showing significant increase in expression of Brn-3a short isoforms.
  
Entity Systemic lupus erythematosus
Note Brn-3a is elevated in approximately 43% of patients with SLE and this correlates with enhanced levels of auto-antibodies to the protein. Increased Brn-3a also correlates with enhanced expression of HSP 90 protein in serum of SLE patients.
  

External links

Nomenclature
HugoPOU4F1
GDBPOU4F1
Entrez_GenePOU4F1  5457  POU class 4 homeobox 1
Cards
AtlasPOU4F1ID44173ch13q31
GeneCardsPOU4F1
EnsemblPOU4F1 [Search_View]   ENSG00000152192 [Gene_View]
GenatlasPOU4F1
GeneLynxPOU4F1
eGenomePOU4F1
euGene5457
Genomic and cartography
GoldenPathPOU4F1  -  13q31.1   chr13:78071233-78075696 -  13q31.1   [Description]    (hg18-Mar_2006)
EnsemblPOU4F1 - 13q31.1 [CytoView]
NCBIMapview
OMIMDisease map [OMIM]
HomoloGenePOU4F1
Gene and transcription
GenbankBC148330 [ ENTREZ ]
GenbankBC148792 [ ENTREZ ]
GenbankBM714015 [ ENTREZ ]
GenbankBM726529 [ ENTREZ ]
GenbankL20433 [ ENTREZ ]
RefSeqNM_006237 [ SRS ]    NM_006237 [ ENTREZ ]
RefSeqAC_000056 [ SRS ]    AC_000056 [ ENTREZ ]
RefSeqNC_000013 [ SRS ]    NC_000013 [ ENTREZ ]
RefSeqNT_024524 [ SRS ]    NT_024524 [ ENTREZ ]
RefSeqNW_925506 [ SRS ]    NW_925506 [ ENTREZ ]
AceViewPOU4F1 AceView - NCBI
UnigeneHs.654522 [ SRS ]    Hs.654522 [ NCBI ]     HS654522 [ spliceNest ]
Fast-db7053 (alternative variants)
Protein : pattern, domain, 3D structure
SwissProtQ01851 [ SRS]    Q01851 [ EXPASY ]     Q01851 [ INTERPRO ]
PrositePS00027 HOMEOBOX_1 [ SRS ]    PS00027 HOMEOBOX_1 [ Expasy ]
PrositePS50071 HOMEOBOX_2 [ SRS ]    PS50071 HOMEOBOX_2 [ Expasy ]
PrositePS00035 POU_1 [ SRS ]    PS00035 POU_1 [ Expasy ]
PrositePS00465 POU_2 [ SRS ]    PS00465 POU_2 [ Expasy ]
PrositePS51179 POU_3 [ SRS ]    PS51179 POU_3 [ Expasy ]
InterproIPR001356 Homeobox [ SRS ]    IPR001356 Homeobox [ EBI ]
InterproIPR012287 Homeodomain-rel [ SRS ]    IPR012287 Homeodomain-rel [ EBI ]
InterproIPR013847 POU [ SRS ]    IPR013847 POU [ EBI ]
InterproIPR015584 POU_4_related [ SRS ]    IPR015584 POU_4_related [ EBI ]
InterproIPR000327 POU_specific [ SRS ]    IPR000327 POU_specific [ EBI ]
CluSTrQ01851
PfamPF00046 Homeobox [ SRS ]    PF00046 Homeobox [ Sanger ]    pfam00046 [ NCBI-CDD ]
PfamPF00157 Pou [ SRS ]    PF00157 Pou [ Sanger ]    pfam00157 [ NCBI-CDD ]
SmartSM00389 HOX [EMBL]
SmartSM00352 POU [EMBL]
ProdomPD000010 Homeobox[INRA-Toulouse]
ProdomQ01851 PO4F1_HUMAN [ Domain structure ]   Q01851 PO4F1_HUMAN  [ sequences sharing at least 1 domain ]
ProdomPD000010[INRA-Toulouse]
ProdomQ01851 PO4F1_HUMAN [ Domain structure ]   Q01851 PO4F1_HUMAN  [ sequences sharing at least 1 domain ]
BlocksQ01851
HPRD03379
Protein Interaction databases
DIPQ01851
IntActQ01851
Polymorphism : SNP, mutations, diseases
OMIM601632    [ map ]   
GENECLINICS601632
SNPPOU4F1 [dbSNP-NCBI]  
SNPNM_006237 [SNP-NCI]  
SNPPOU4F1 [GeneSNPs - Utah]  POU4F1] [HGBASE - SRS]
HAPMAPPOU4F1 [HAPMAP]  
HGMDPOU4F1
General knowledge
Family BrowserPOU4F1 [UCSC Family Browser]
SOURCENM_006237
SMDHs.654522
SAGEHs.654522
GOsuckling behavior [Amigo]  suckling behavior
GOtranscription factor activity [Amigo]  transcription factor activity
GOprotein binding [Amigo]  protein binding
GOnucleus [Amigo]  nucleus
GOregulation of transcription from RNA polymerase II promoter [Amigo]  regulation of transcription from RNA polymerase II promoter
GOmulticellular organismal development [Amigo]  multicellular organismal development
GOaxonogenesis [Amigo]  axonogenesis
GOsynaptogenesis [Amigo]  synaptogenesis
GOcell migration in hindbrain [Amigo]  cell migration in hindbrain
GOcentral nervous system neuron differentiation [Amigo]  central nervous system neuron differentiation
GOpositive regulation of apoptosis [Amigo]  positive regulation of apoptosis
GOsequence-specific DNA binding [Amigo]  sequence-specific DNA binding
GOperipheral nervous system neuron differentiation [Amigo]  peripheral nervous system neuron differentiation
GOproprioception during equilibrioception [Amigo]  proprioception during equilibrioception
PubGenePOU4F1
TreeFamPOU4F1
CTD5457 [Comparative ToxicoGenomics Database]
Other databases
Probes
ProbePOU4F1 Related clones (RZPD - Berlin)
PubMed
PubMed20 Pubmed reference(s) in LocusLink

Bibliography

Expression of a large family of POU-domain regulatory genes in mammalian brain development.
He X, Treacy MN, Simmons DM, Ingraham HA, Swanson LW, Rosenfeld MG
Nature. 1989 ; 340 (6228) : 35-41.
PMID 2739723
 
A novel POU homeodomain gene specifically expressed in cells of the developing mammalian nervous system.
Collum RG, Fisher PE, Datta M, Mellis S, Thiele C, Huebner K, Croce CM, Israel MA, Theil T, Moroy T
Nucleic acids research. 1992 ; 20 (18) : 4919-4925.
PMID 1357630
 
A novel POU family transcription factor is closely related to Brn-3 but has a distinct expression pattern in neuronal cells.
Lillycrop KA, Budrahan VS, Lakin ND, Terrenghi G, Wood JN, Polak JM, Latchman DS
Nucleic acids research. 1992 ; 20 (19) : 5093-5096.
PMID 1383937
 
Differential expression of four members of the POU family of proteins in activated and phorbol 12-myristate 13-acetate-treated Jurkat T cells.
Bhargava AK, Li Z, Weissman SM
Proceedings of the National Academy of Sciences of the United States of America. 1993 ; 90 (21) : 10260-10264.
PMID 8234287
 
The DNA target site for the Brn-3 POU family transcription factors can confer responsiveness to cyclic AMP and removal of serum in neuronal cells.
Budhram-Mahadeo V, Theil T, Morris PJ, Lillycrop KA, Moroy T, Latchman DS
Nucleic acids research. 1994 ; 22 (15) : 3092-3098.
PMID 8065921
 
The levels of the antagonistic POU family transcription factors Brn-3a and Brn-3b in neuronal cells are regulated in opposite directions by serum growth factors.
Budhram-Mahadeo V, Lillycrop KA, Latchman DS
Neuroscience letters. 1995 ; 185 (1) : 48-51.
PMID 7731552
 
Activation of the alpha-internexin promoter by the Brn-3a transcription factor is dependent on the N-terminal region of the protein.
Budhram-Mahadeo V, Morris PJ, Lakin ND, Theil T, Ching GY, Lillycrop KA, Mry T, Liem RK, Latchman DS
The Journal of biological chemistry. 1995 ; 270 (6) : 2853-2858.
PMID 7852360
 
Brn-3.0 expression identifies early post-mitotic CNS neurons and sensory neural precursors.
Fedtsova NG, Turner EE
Mechanisms of development. 1995 ; 53 (3) : 291-304.
PMID 8645597
 
Regulation of neurite outgrowth and SNAP-25 gene expression by the Brn-3a transcription factor.
Lakin ND, Morris PJ, Theil T, Sato TN, Mry T, Wilson MC, Latchman DS
The Journal of biological chemistry. 1995 ; 270 (26) : 15858-15863.
PMID 7797590
 
Activation of the herpes simplex virus immediate-early gene promoters by neuronally expressed POU family transcription factors.
Lillycrop KA, Liu YZ, Theil T, Mry T, Latchman DS
The Biochemical journal. 1995 ; 307 ( Pt 2) : 581-584.
PMID 7733899
 
The neuronal nicotinic acetylcholine receptor alpha 2 subunit gene promoter is activated by the Brn-3b POU family transcription factor and not by Brn-3a or Brn-3c.
Milton NG, Bessis A, Changeux JP, Latchman DS
The Journal of biological chemistry. 1995 ; 270 (25) : 15143-15147.
PMID 7797498
 
The different activities of the two activation domains of the Brn-3a transcription factor are dependent on the context of the binding site.
Budhram-Mahadeo V, Morris PJ, Lakin ND, Dawson SJ, Latchman DS
The Journal of biological chemistry. 1996 ; 271 (15) : 9108-9113.
PMID 8621561
 
Activation and repression of gene expression by POU family transcription factors.
Latchman DS
Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 1996 ; 351 (1339) : 511-515.
PMID 8735273
 
Alternative splicing of the Brn-3a and Brn-3b transcription factor RNAs is regulated in neuronal cells.
Liu YZ, Dawson SJ, Latchman DS
Journal of molecular neuroscience : MN. 1996 ; 7 (1) : 77-85.
PMID 8835784
 
Requirement for Brn-3.0 in differentiation and survival of sensory and motor neurons.
McEvilly RJ, Erkman L, Luo L, Sawchenko PE, Ryan AF, Rosenfeld MG
Nature. 1996 ; 384 (6609) : 574-577.
PMID 8955272
 
Differential regulation of neuronal nicotinic acetylcholine receptor subunit gene promoters by Brn-3 POU family transcription factors.
Milton NG, Bessis A, Changeux JP, Latchman DS
The Biochemical journal. 1996 ; 317 ( Pt 2) : 419-423.
PMID 8713067
 
Differential regulation of genes encoding synaptic proteins by members of the Brn-3 subfamily of POU transcription factors.
Morris PJ, Lakin ND, Dawson SJ, Ryabinin AE, Kilimann MW, Wilson MC, Latchman DS
Brain research. Molecular brain research. 1996 ; 43 (1-2) : 279-285.
PMID 9037543
 
The functionally antagonistic POU family transcription factors Brn-3a and Brn-3b show opposite changes in expression during the growth arrest and differentiation of human neuroblastoma cells.
Smith MD, Latchman DS
International journal of cancer. Journal international du cancer. 1996 ; 67 (5) : 653-660.
PMID 8782654
 
POU-domain factor expression in the trigeminal ganglion and implications for herpes virus regulation.
Turner EE, Fedtsova N, Rosenfeld MG
Neuroreport. 1996 ; 7 (18) : 2829-2832.
PMID 9116190
 
Targeted deletion of the mouse POU domain gene Brn-3a causes selective loss of neurons in the brainstem and trigeminal ganglion, uncoordinated limb movement, and impaired suckling.
Xiang M, Gan L, Zhou L, Klein WH, Nathans J
Proceedings of the National Academy of Sciences of the United States of America. 1996 ; 93 (21) : 11950-11955.
PMID 8876243
 
High expression of the POU factor Brn3a in aggressive neuroendocrine tumors.
Leblond-Francillard M, Picon A, Bertagna X, de Keyzer Y
The Journal of clinical endocrinology and metabolism. 1997 ; 82 (1) : 89-94.
PMID 8989239
 
The Brn-3a transcription factor induces neuronal process outgrowth and the coordinate expression of genes encoding synaptic proteins.
Smith MD, Dawson SJ, Latchman DS
Molecular and cellular biology. 1997 ; 17 (1) : 345-354.
PMID 8972215
 
Coordinate induction of the three neurofilament genes by the Brn-3a transcription factor.
Smith MD, Morris PJ, Dawson SJ, Schwartz ML, Schlaepfer WW, Latchman DS
The Journal of biological chemistry. 1997 ; 272 (34) : 21325-21333.
PMID 9261145
 
Role of the Brn-3 family of POU-domain genes in the development of the auditory/vestibular, somatosensory, and visual systems.
Xiang M, Gan L, Li D, Zhou L, Chen ZY, Wagner D, O'Malley BW Jr, Klein W, Nathans J
Cold Spring Harbor symposia on quantitative biology. 1997 ; 62 : 325-336.
PMID 9598366
 
The Brn-3a transcription factor.
Latchman DS
The international journal of biochemistry & cell biology. 1998 ; 30 (11) : 1153-1157.
PMID 9839440
 
Activation of the iNOS gene promoter by Brn-3 POU family transcription factors is dependent upon the octamer motif in the promoter.
Gay RD, Dawson SJ, Murphy WJ, Russell SW, Latchman DS
Biochimica et biophysica acta. 1998 ; 1443 (3) : 315-322.
PMID 9878805
 
The HPV-activating cellular transcription factor Brn-3a is overexpressed in CIN3 cervical lesions.
Ndisdang D, Morris PJ, Chapman C, Ho L, Singer A, Latchman DS
The Journal of clinical investigation. 1998 ; 101 (8) : 1687-1692.
PMID 9541499
 
The N-terminal domain unique to the long form of the Brn-3a transcription factor is essential to protect neuronal cells from apoptosis and for the activation of Bbcl-2 gene expression.
Smith MD, Dawson SJ, Boxer LM, Latchman DS
Nucleic acids research. 1998 ; 26 (18) : 4100-4107.
PMID 9722627
 
NT-3 regulates expression of Brn3a but not Brn3b in developing mouse trigeminal sensory neurons.
Wyatt S, Ensor L, Begbie J, Ernfors P, Reichardt LF, Latchman DS
Brain research. Molecular brain research. 1998 ; 55 (2) : 254-264.
PMID 9582431
 
p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor.
Budhram-Mahadeo V, Morris PJ, Smith MD, Midgley CA, Boxer LM, Latchman DS
The Journal of biological chemistry. 1999 ; 274 (21) : 15237-15244.
PMID 10329733
 
POU domain factor Brn-3a controls the differentiation and survival of trigeminal neurons by regulating Trk receptor expression.
Huang EJ, Zang K, Schmidt A, Saulys A, Xiang M, Reichardt LF
Development (Cambridge, England). 1999 ; 126 (13) : 2869-2882.
PMID 10357931
 
The Brn-3a transcription factor plays a critical role in regulating human papilloma virus gene expression and determining the growth characteristics of cervical cancer cells.
Ndisang D, Budhram-Mahadeo V, Latchman DS
The Journal of biological chemistry. 1999 ; 274 (40) : 28521-28527.
PMID 10497216
 
Regulation of NGFI-A (Egr-1) gene expression by the POU domain transcription factor Brn-3a.
Smith MD, Ensor EA, Stohl L, Wagner JA, Latchman DS
Brain research. Molecular brain research. 1999 ; 74 (1-2) : 117-125.
PMID 10640682
 
Autoregulatory sequences are revealed by complex stability screening of the mouse brn-3.0 locus.
Trieu M, Rhee JM, Fedtsova N, Turner EE
The Journal of neuroscience : the official journal of the Society for Neuroscience. 1999 ; 19 (15) : 6549-6558.
PMID 10414983
 
Widespread elevated expression of the human papilloma virus (HPV)-activating cellular transcription factor Brn-3a in the cervix of women with CIN3 (cervical intraepithelial neoplasia stage 3).
Ndisang D, Budhram-Mahadeo V, Singer A, Latchman DS
Clinical science (London, England : 1979). 2000 ; 98 (5) : 601-602.
PMID 10781392
 
The closely related POU family transcription factors Brn-3a and Brn-3b are expressed in distinct cell types in the testis.
Budhram-Mahadeo V, Moore A, Morris PJ, Ward T, Weber B, Sassone-Corsi P, Latchman DS
The international journal of biochemistry & cell biology. 2001 ; 33 (10) : 1027-1039.
PMID 11470235
 
Defects in sensory axon growth precede neuronal death in Brn3a-deficient mice.
Eng SR, Gratwick K, Rhee JM, Fedtsova N, Gan L, Turner EE
The Journal of neuroscience : the official journal of the Society for Neuroscience. 2001 ; 21 (2) : 541-549.
PMID 11160433
 
The BRN-3A transcription factor protects sensory but not sympathetic neurons from programmed cell death/apoptosis.
Ensor E, Smith MD, Latchman DS
The Journal of biological chemistry. 2001 ; 276 (7) : 5204-5212.
PMID 11053412
 
Signals from the ventral midline and isthmus regulate the development of Brn3.0-expressing neurons in the midbrain.
Fedtsova N, Turner EE
Mechanisms of development. 2001 ; 105 (1-2) : 129-144.
PMID 11429288
 
Brn3a is a transcriptional regulator of soma size, target field innervation and axon pathfinding of inner ear sensory neurons.
Huang EJ, Liu W, Fritzsch B, Bianchi LM, Reichardt LF, Xiang M
Development (Cambridge, England). 2001 ; 128 (13) : 2421-2432.
PMID 11493560
 
The Brn-3a transcription factor plays a key role in regulating the growth of cervical cancer cells in vivo.
Ndisang D, Budhram-Mahadeo V, Pedley B, Latchman DS
Oncogene. 2001 ; 20 (35) : 4899-4903.
PMID 11521202
 
Brn-3a activates the expression of Bcl-x(L) and promotes neuronal survival in vivo as well as in vitro.
Smith MD, Melton LA, Ensor EA, Packham G, Anderson P, Kinloch RA, Latchman DS
Molecular and cellular neurosciences. 2001 ; 17 (3) : 460-470.
PMID 11273642
 
The Brn-3a transcription factor inhibits the pro-apoptotic effect of p53 and enhances cell cycle arrest by differentially regulating the activity of the p53 target genes encoding Bax and p21(CIP1/Waf1).
Budram-Mahadeo V, Morris PJ, Latchman DS
Oncogene. 2002 ; 21 (39) : 6123-6131.
PMID 12203124
 
The Brn-3a POU family transcription factor stimulates p53 gene expression in human and mouse tumour cells.
Budhram-Mahadeo V, Morris P, Ndisang D, Irshad S, Lozano G, Pedley B, Latchman DS
Neuroscience letters. 2002 ; 334 (1) : 1-4.
PMID 12431761
 
Accessibility of phosphates in domain I of 23 S rRNA in the ribosomal 50 S subunit as detected by R(P) phosphorothioates.
Maivli U, Pulk A, Loogvli EL, Remme J
Biochimica et biophysica acta. 2002 ; 1579 (1) : 1-7.
PMID 12401213
 
Effect of Brn-3a deficiency on nociceptors and low-threshold mechanoreceptors in the trigeminal ganglion.
Ichikawa H, Mo Z, Xiang M, Sugimoto T
Brain research. Molecular brain research. 2002 ; 104 (2) : 240-245.
PMID 12225879
 
Distinct promoter elements mediate the co-operative effect of Brn-3a and p53 on the p21 promoter and their antagonism on the Bax promoter.
Perez-Sanchez C, Budhram-Mahadeo VS, Latchman DS
Nucleic acids research. 2002 ; 30 (22) : 4872-4880.
PMID 12433990
 
The pro-oncoprotein EWS (Ewing's Sarcoma protein) interacts with the Brn-3a POU transcription factor and inhibits its ability to activate transcription.
Thomas GR, Latchman DS
Cancer biology & therapy. 2002 ; 1 (4) : 428-432.
PMID 12432261
 
Brn3a regulation of TrkA/NGF receptor expression in developing sensory neurons.
Ma L, Lei L, Eng SR, Turner E, Parada LF
Development (Cambridge, England). 2003 ; 130 (15) : 3525-3534.
PMID 12810599
 
Doppel expression is regulated by the Brn-3a and Brn-3b transcription factors.
Calissano M, Ensor E, Brown DR, Latchman DS
Neuroreport. 2004 ; 15 (3) : 483-486.
PMID 15094508
 
Coordinated regulation of gene expression by Brn3a in developing sensory ganglia.
Eng SR, Lanier J, Fedtsova N, Turner EE
Development (Cambridge, England). 2004 ; 131 (16) : 3859-3870.
PMID 15253936
 
Regulation of Hsp27 expression and cell survival by the POU transcription factor Brn3a.
Farooqui-Kabir SR, Budhram-Mahadeo V, Lewis H, Latchman DS, Marber MS, Heads RJ
Cell death and differentiation. 2004 ; 11 (11) : 1242-1244.
PMID 15272315
 
Distinct domains of Brn-3a regulate apoptosis and neurite outgrowth in vivo.
Faulkes DJ, Ensor E, Le Rouzic E, Latchman DS
Neuroreport. 2004 ; 15 (9) : 1421-1425.
PMID 15194866
 
The effects of Brn-3a on neuronal differentiation and apoptosis are differentially modulated by EWS and its oncogenic derivative EWS/Fli-1.
Gascoyne DM, Thomas GR, Latchman DS
Oncogene. 2004 ; 23 (21) : 3830-3840.
PMID 15021903
 
Coexpression of Brn-3a POU protein with p53 in a population of neuronal progenitor cells is associated with differentiation and protection against apoptosis.
Hudson CD, Podesta J, Henderson D, Latchman DS, Budhram-Mahadeo V
Journal of neuroscience research. 2004 ; 78 (6) : 803-814.
PMID 15532030
 
EWS differentially activates transcription of the Brn-3a long and short isoform mRNAs from distinct promoters.
Thomas GR, Faulkes DJ, Gascoyne D, Latchman DS
Biochemical and biophysical research communications. 2004 ; 318 (4) : 1045-1051.
PMID 15147979
 
Phosphorylation of the Brn-3a transcription factor is modulated during differentiation and regulates its functional activity.
Calissano M, Faulkes D, Latchman DS
Brain research. Molecular brain research. 2005 ; 141 (1) : 10-18.
PMID 16126301
 
Brn-3a transcription factor blocks p53-mediated activation of proapoptotic target genes Noxa and Bax in vitro and in vivo to determine cell fate.
Hudson CD, Morris PJ, Latchman DS, Budhram-Mahadeo VS
The Journal of biological chemistry. 2005 ; 280 (12) : 11851-11858.
PMID 15598651
 
Brn-3a deficiency increases tyrosine hydroxylase-immunoreactive neurons in the dorsal root ganglion.
Ichikawa H, Mo Z, Xiang M, Sugimoto T
Brain research. 2005 ; 1036 (1-2) : 192-195.
PMID 15725417
 
Brn-3a is required for the generation of proprioceptors in the mesencephalic trigeminal tract nucleus.
Ichikawa H, Qiu F, Xiang M, Sugimoto T
Brain research. 2005 ; 1053 (1-2) : 203-206.
PMID 16040009
 
Effect of Brn-3a deficiency on primary nociceptors in the trigeminal ganglion.
Ichikawa H, Schulz S, Hllt V, Mo Z, Xiang M, Sugimoto T
Neuroscience research. 2005 ; 51 (4) : 445-451.
PMID 15740807
 
Elevated expression of the Brn-3a and Brn-3b transcription factors in systemic lupus erythematosus correlates with antibodies to Brn-3 and overexpression of Hsp90.
Ripley BJ, Rahman MA, Isenberg DA, Latchman DS
Arthritis and rheumatism. 2005 ; 52 (4) : 1171-1179.
PMID 15818685
 
Brn-3a neuronal transcription factor functional expression in human prostate cancer.
Diss JK, Faulkes DJ, Walker MM, Patel A, Foster CS, Budhram-Mahadeo V, Djamgoz MB, Latchman DS
Prostate cancer and prostatic diseases. 2006 ; 9 (1) : 83-91.
PMID 16276351
 
Differential regulation of different human papilloma virus variants by the POU family transcription factor Brn-3a.
Ndisang D, Faulkes DJ, Gascoyne D, Lee SA, Ripley BJ, Sindos M, Singer A, Budhram-Mahadeo V, Cason J, Latchman DS
Oncogene. 2006 ; 25 (1) : 51-60.
PMID 16247485
 
Brn3a target gene recognition in embryonic sensory neurons.
Lanier J, Quina LA, Eng SR, Cox E, Turner EE
Developmental biology. 2007 ; 302 (2) : 703-716.
PMID 17196582
 
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Contributor(s)

Written12-2007Vishwanie Budhram-Mahadeo, David S Latchman
Medical Molecular Biology Unit, Institute of Child Health, 30 Guilford St, London WC 1N1 EH, UK

Citation

This paper should be referenced as such :
Budhram-Mahadeo V, Latchman DS . POU4F1 (POU class 4 homeobox 1). Atlas Genet Cytogenet Oncol Haematol. December 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/POU4F1ID44173ch13q31.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jul 2 08:26:08 2008


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