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

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
202019262010Human variation in alcohol response is influenced by variation in neuronal signaling genes.45
262145922015Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.43
75560721995The rat hepatic leukemia factor (HLF) gene encodes two transcriptional activators with distinct circadian rhythms, tissue distributions and target preferences.26
171833642007Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19.26
311182472019Oncofetal HLF transactivates c-Jun to promote hepatocellular carcinoma development and sorafenib resistance.15
182390672008Thyroid hormone induces hypoxia-inducible factor 1alpha gene expression through thyroid hormone receptor beta/retinoid x receptor alpha-dependent activation of hepatic leukemia factor.14
127000342003E2A basic helix-loop-helix transcription factors in human leukemia.12
210720442011The E2A-HLF oncogenic fusion protein acts through Lmo2 and Bcl-2 to immortalize hematopoietic progenitors.12
275220032016HLF/miR-132/TTK axis regulates cell proliferation, metastasis and radiosensitivity of glioma cells.12
205196282010Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19).10

Citation

Franck Viguié

HLF (hepatic leukemia factor)

Atlas Genet Cytogenet Oncol Haematol. 1999-09-01

Online version: http://atlasgeneticsoncology.org/gene/47/hlf