Download Gene Section CBFb (subunit b of core binding factor)

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in Oncology and Haematology
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CBFb (subunit b of core binding factor)
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
(JLH)
Published in Atlas Database: June 1999
Online updated version : http://AtlasGeneticsOncology.org/Genes/CBFbID45.html
DOI: 10.4267/2042/37526
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 1999 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Description
Identity
6 exons; 50 kb.
Other names: PEBP2b (polyomavirus enhancer
binding protein b)
HGNC (Hugo): CBFB
Location: 16q22
Transcription
Alternate splicing at cDNA positions 495 (in exon 5)
and 526.
Protein
Description
2 alternative forms of 182 and 187 amino acids with the
first 165 N-term identical amino acids and different Cterm; 22 kDa.
Expression
Wide.
Localisation
Cytoplasmic when not dimerized.
Function
CBF is a heterodimer comprising the subunit b (CBFb)
and the subunit CBFa (3 CBFa genes are known, of
which is CBFa2, also called AML1, involved in the
well known t(8;21), t(12;21), and in other leukaemias);
CBF binds to a core motif of the DNA (herein the
name); CBFb by itself does not contain any known
DNA binding motif or any transcriptional activation
domain; CBFa binds to DNA; CBFb increases CBFa's
affinity to DNA by 5 to 10 fold; CBF is a transcription
factor which regulates the expression of myeloid and Tcell specific genes such as: GM-CSF, M-CSFR, IL3, TCell receptors TCRA-D, TCRB and TCRG; CBF
cooperate with various tissue specific factors to activate
these lineage-restricted transcriptions; homozygous
knock down of either CBFb or CBFa results in
embryonic lethality, showing that they are essential for
fetal liver hematopoiesis.
CBFB (16q22) - Courtesy Mariano Rocchi, Resources for
Molecular Cytogenetics.
DNA/RNA
CBFβ and CBFα association to bind on the DNA core site:
Py-G-Py-G-G-T-Py.
Atlas Genet Cytogenet Oncol Haematol. 1999; 3(3)
124
CBFb (subunit b of core binding factor)
Huret JL
acute myelomonocytic leukemia. Blood. 1993 Aug 1;82(3):71621
Homology
Highly conserved through the species.
Ogawa E, Inuzuka M, Maruyama M, Satake M, Naito-Fujimoto
M, Ito Y, Shigesada K. Molecular cloning and characterization
of PEBP2 beta, the heterodimeric partner of a novel Drosophila
runt-related DNA binding protein PEBP2 alpha. Virology. 1993
May;194(1):314-31
Implicated in
inv(16)(p13q22), t(16;16)(p13;q22), and
del(16)(q22) in acute non lymphoblastic
leukaemia (ANLL) or myelodysplastic
syndromes (MDS)
--> CBFb - MYH11
Ogawa E, Maruyama M, Kagoshima H, Inuzuka M, Lu J,
Satake M, Shigesada K, Ito Y. PEBP2/PEA2 represents a
family of transcription factors homologous to the products of
the Drosophila runt gene and the human AML1 gene. Proc Natl
Acad Sci U S A. 1993 Jul 15;90(14):6859-63
Wang S, Wang Q, Crute BE, Melnikova IN, Keller SR, Speck
NA. Cloning and characterization of subunits of the T-cell
receptor and murine leukemia virus enhancer core-binding
factor. Mol Cell Biol. 1993 Jun;13(6):3324-39
Disease
Nearly pathognomonic of M4eo-ANLL:
eosinophilia; frequent CNS involvement.
with
Castilla LH, Wijmenga C, Wang Q, Stacy T, Speck NA,
Eckhaus M, Marín-Padilla M, Collins FS, Wynshaw-Boris A, Liu
PP. Failure of embryonic hematopoiesis and lethal
hemorrhages in mouse embryos heterozygous for a knockedin leukemia gene CBFB-MYH11. Cell. 1996 Nov 15;87(4):68796
Prognosis
High CR rate; better prognosis than most other ANLL.
Cytogenetics
The 3 chromosome anomalies are variants of each
other.
van der Reijden BA, van Ommen GJ, Hagemeijer A, Breuning
MH. Acute myelogenous leukemia: a disorder of gene splicing?
Leukemia. 1996 Feb;10(2):204-6
Hybrid/Mutated gene
5' CBFb - 3' MYH11.
Abnormal protein
Wang Q, Stacy T, Miller JD, Lewis AF, Gu TL, Huang X,
Bushweller JH, Bories JC, Alt FW, Ryan G, Liu PP, WynshawBoris A, Binder M, Marín-Padilla M, Sharpe AH, Speck NA.
The CBFbeta subunit is essential for CBFalpha2 (AML1)
function in vivo. Cell. 1996 Nov 15;87(4):697-708
The N-trem and most of CBFb is fused to the MYH11
C-term with its multimerization domain.
References
This article should be referenced as such:
Liu P, Claxton DF, Marlton P, Hajra A, Siciliano J, Freedman
M, Chandrasekharappa SC, Yanagisawa K, Stallings RL,
Collins FS. Identification of yeast artificial chromosomes
containing the inversion 16 p-arm breakpoint associated with
Atlas Genet Cytogenet Oncol Haematol. 1999; 3(3)
Huret JL. CBFb (subunit b of core binding factor). Atlas Genet
Cytogenet Oncol Haematol. 1999; 3(3):124-125.
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