HLF (hepatic leukemia factor)

1999-09-01   Franck Viguié  

Laboratoire de Cytogenetique - Service dHematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

Identity

HGNC
LOCATION
17q22
LOCUSID
ALIAS
-
FUSION GENES

DNA/RNA

Atlas Image
DNA diagram

Transcription

3.9 kb

Proteins

Atlas Image
Protein diagram

Description

295 amino acids, MW 43 kDa

Expression

HLF is normally expressed in hepatocytes and liver-derived cell lines, and, to a lesser extent, in lung, kidney and neurons of the central nervous system; it is not expressed in hematopoietic tissues or cell lines

Localisation

nuclear

Function

the normal function of HLF is largely unknown; HLF is a member of the PAR (proline and acidic amino acid-rich region) subfamily of b/ZIP (basic region leucine zipper) transcription factors; PAR and b/ZIP proteins bind to the DNA as dimers; HLF acts as a transcriptionnal transactivator; there are evidences that HLF protein transactivates factor VIII and factor IX genes, by binding as a homodimer (HLF/HLF) or a heterodimer with one albumin D-element binding protein sub unit (HLF/DBP), to multiple sites in the promoter of these genes; in the mouse central nervous system ontogeny, HLF expression increases markedly with synaptogenesis, suggesting that HLF plays a role in the function of adult differentiated neurons

Homology

other members of the b/ZIP PAR subfamily; in mammals: albumin D-element binding protein (DBP) and thyrotroph embryonic factor / vitellogenin gene binding protein (TEF/VBP); like HLF, they are transcription activators; the three proteins have an ability to form heterodimers with one another through the leucine-zipper domain; in other species : vitellogenin binding protein (VBP) in the chicken and Ces-2 gene in the nematode Caenorhabditis elegans

Implicated in

Entity name
t(17;19)(q22;p13) in acute lymphoblastic leukemia --> E2A - HLF fusion gene
Disease
childhood pro-B cell acute lymphoblastic leukemia
Prognosis
poor prognosis is likely
Fusion protein
fusion encodes a protein which contains the AD1 and AD2 transactivation domains of E2A, linked to the bZIP DNA binding / protein dimerization region of HLF
Oncogenesis
E2A-HLF alters the apoptotic pathway of pro-B lymphocytic cells, leading to the survival of defective cells that would normally be eliminated; it is to be noted that, in normal tissues, there is no evidence in favour of a role of native HLF in apoptosis regulation

Article Bibliography

Pubmed IDLast YearTitleAuthors
100735761999Enhanced binding of HLF/DBP heterodimers represents one mechanism of PAR protein transactivation of the factor VIII and factor IX genes.Begbie M et al
100230251999Expression patterns of the hepatic leukemia factor gene in the nervous system of developing and adult mice.Hitzler JK et al
86082071996Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis.Hunger SP et al
86398291996The proto-oncogene HLF and the related basic leucine zipper protein TEF display highly similar DNA-binding and transcriptional regulatory properties.Hunger SP et al
13861621992Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia.Inaba T et al
90322681997Cell transformation mediated by homodimeric E2A-HLF transcription factors.Inukai T et al
95712071998Regulation of the DBP promoter by PAR proteins and in leukemic cells bearing an E2A/HLF translocation.Newcombe K et al

Other Information

Locus ID:

NCBI: 3131
MIM: 142385
HGNC: 4977
Ensembl: ENSG00000108924

Variants:

dbSNP: 3131
ClinVar: 3131
TCGA: ENSG00000108924
COSMIC: HLF

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000108924ENST00000226067Q16534
ENSG00000108924ENST00000430986Q16534
ENSG00000108924ENST00000570962I3L386
ENSG00000108924ENST00000572002I3L4R4
ENSG00000108924ENST00000573945Q16534
ENSG00000108924ENST00000575345Q16534

Expression (GTEx)

0
10
20
30
40
50
60
70
80

References

Pubmed IDYearTitleCitations
369586942023m6A RNA methylation-mediated upregulation of HLF promotes intrahepatic cholangiocarcinoma progression by regulating the FZD4/β-catenin signaling pathway.6
377097682023HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway.1
377127642023Tensin 1 regulated by hepatic leukemia factor represses the progression of prostate cancer.0
369586942023m6A RNA methylation-mediated upregulation of HLF promotes intrahepatic cholangiocarcinoma progression by regulating the FZD4/β-catenin signaling pathway.6
377097682023HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway.1
377127642023Tensin 1 regulated by hepatic leukemia factor represses the progression of prostate cancer.0
349916592022HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk.60
363749582022CircCHD2/miR-200b-3p/HLF Axis Promotes Liver Cirrhosis.4
349916592022HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk.60
363749582022CircCHD2/miR-200b-3p/HLF Axis Promotes Liver Cirrhosis.4
339793202021Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma.12
344997172021HLF expression defines the human hematopoietic stem cell state.24
348766312021FLT3-ITD allelic ratio and HLF expression predict FLT3 inhibitor efficacy in adult AML.5
349256452021Integrative Molecular Analyses of an Individual Transcription Factor-Based Genomic Model for Lung Cancer Prognosis.2
339793202021Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma.12

Citation

Franck Viguié

HLF (hepatic leukemia factor)

Atlas Genet Cytogenet Oncol Haematol. 1999-09-01

Online version: http://atlasgeneticsoncology.org/gene/47/hlf-(hepatic-leukemia-factor)