Download Gene Section BCL2L12 (BCL2-like 12 (proline-rich)) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
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BCL2L12 (BCL2-like 12 (proline-rich))
Christos Kontos, Hellinida Thomadaki, Andreas Scorilas
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens. 157 01,
Panepistimiopolis, Athens, Greece (CK, HT, AS)
Published in Atlas Database: August 2008
Online updated version : http://AtlasGeneticsOncology.org/Genes/BCL2L12ID773ch19q13.html
DOI: 10.4267/2042/44508
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2009 Atlas of Genetics and Cytogenetics in Oncology and Haematology
protein, and five consensus PXXP tetrapeptide
sequences.
BCL2L12 protein also includes various putative
posttranslational modification sites. There are
numerous potential sites for O-glycosylation.
Furthermore, several possible sites of phosphorylation
have been identified for cAMP-dependent protein
kinase, protein kinase C, and casein kinase 2.
In addition, several N-myristoylation sites have been
predicted. The BCL2L12 protein was found to have
proline-rich sites. One PPPP site as well as five PP
amino acid sites are present in this protein. Eight
putative PXXP motifs were also identified. Proline-rich
motifs are characterized by the presence of the
consensus PXXP tetrapeptide, found in all proline-rich
proteins identified to date. It is known that SH3
domains recognize proline-rich sequences and that all
known SH3-binding proteins contain proline-rich
regions with at least one PXXP motif. Proline-rich
domains have been identified in a number of diverse
proteins such as epidermal growth factors,
phosphatidylinositol 3-kinase, and, more recently, the
small GTPase RRAS protein and members of the
RRAS superfamily such as the TC21 protein.
Moreover, the amino acid loop (PPSPEP) at positions
271-276 of the BCL2L12 protein is identical with the
PXXP motif present in the RRAS and TC21
oncogenes. This motif is required for integrin
activation.
The splice variant BCL2L12-A is expected to encode a
truncated protein of 176 amino acids with five PP
proline sites, two putative PXXP motifs, and no BH2
homology domain.
Identity
Other names: BPR; MGC120313; MGC120314;
MGC120315
HGNC (Hugo): BCL2L12
Location: 19q13.3
Local order: Telomere to centromere.
DNA/RNA
Description
Spanning 8.8 kb of genomic DNA, the BCL2L12 gene
consists of 6 introns and 7 exons.
Transcription
The BCL2L12 gene has three splice variants with
differences in exon 3. The predominant form is 1855 bp
and encodes the full-length protein. The second splice
variant lacks exon 3, which consists of 143 bp, thus
resulting in no ORF. The third splice variant lacks 3 bp
at the beginning of exon 3 and encodes a protein having
one amino acid residue less than the full-lengh protein.
Pseudogene
Not identified so far.
Protein
Description
The BCL2L12 protein is composed of 334 amino acids,
with a calculated molecular mass of 36.8 kDa and an
isoelectric point of 9.45. The BCL2L12 protein
contains one BH2 and one putative BH3 domain, one
proline-rich region similar to the TC21
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7)
467
BCL2L12 (BCL2-like 12 (proline-rich))
Kontos C, et al.
Expression
References
High levels of BCL2L12 expression are typically found
in glandular epithelia in various organs, such as
gastrointestinal tract and/or breast. Lower BCL2L12
protein expression has been found in prostate tissue.
Scorilas A, Kyriakopoulou L, Yousef GM, Ashworth LK,
Kwamie A, Diamandis EP. Molecular cloning, physical
mapping, and expression analysis of a novel gene, BCL2L12,
encoding a proline-rich protein with a highly conserved BH2
domain of the Bcl-2 family. Genomics. 2001 Mar 1;72(2):21721
Function
BCL2L12 is involved in apoptosis. However, its
proapoptotic or antiapoptotic role in different types of
cells and conditions remains unclear.
Homology
Floros KV, Thomadaki H, Lallas G, Katsaros N, Talieri M,
Scorilas A. Cisplatin-induced apoptosis in HL-60 human
promyelocytic leukemia cells: differential expression of BCL2
and novel apoptosis-related gene BCL2L12. Ann N Y Acad
Sci. 2003 Dec;1010:153-8
Human BCL2L12 shares 98% and 96% identity with
chimpanzee and Rhesus monkey Bcl2l12, respectively,
and 83% identity with rat/mouse Bc2l12 as well.
Talieri M, Diamandis EP, Katsaros N, Gourgiotis D, Scorilas A.
Expression of BCL2L12, a new member of apoptosis-related
genes, in breast tumors. Thromb Haemost. 2003
Jun;89(6):1081-8
Mutations
Floros KV, Thomadaki H, Katsaros N, Talieri M, Scorilas A.
mRNA expression analysis of a variety of apoptosis-related
genes, including the novel gene of the BCL2-family, BCL2L12,
in HL-60 leukemia cells after treatment with carboplatin and
doxorubicin. Biol Chem. 2004 Nov;385(11):1099-103
Note
No germinal or somatic mutations are identified to be
associated with cancer so far.
Mathioudaki K, Scorilas A, Papadokostopoulou A, Xynopoulos
D, Arnogianaki N, Agnanti N, Talieri M. Expression analysis of
BCL2L12, a new member of apoptosis-related genes, in colon
cancer. Biol Chem. 2004 Sep;385(9):779-83
Implicated in
Human Leukemias, Solid Tumors
Floros KV, Talieri M, Scorilas A. Topotecan and methotrexate
alter expression of the apoptosis-related genes BCL2, FAS
and BCL2L12 in leukemic HL-60 cells. Biol Chem. 2006
Dec;387(12):1629-33
Note
Significant alterations of BCL2L12 mRNA expression
have been noticed in HL-60 leukemia cells as well as in
MCF7 breast cancer cells, after treatment with various
antineoplastic agents including cisplatin, carboplatin,
doxorubicin, methotrexate, and etoposide. These
important modulations of BCL2L12 mRNA levels
seem to depend on both the apoptotic inducer and the
specific apoptotic pathway, implying a strong
relationship between alterations in BCL2L12 mRNA
levels and apoptosis.
Expression analysis of the BCL2L12 gene has showed
that BCL2L12 mRNA expression may be considered as
a new prognostic marker for breast cancer, as breast
tumours of lower stage or grade are more often
BCL2L12-positive. Moreover, breast cancer patients
with BCL2L12 mRNA expression are less likely to
relapse or die, in comparison with BCL2L12-negative
patients. Regarding BCL2L12 gene expression in colon
cancer, the BCL2L12-A transcript is overexpressed in
cancer tissues as compared to their normal mucosa
counterparts. BCL2L12-A mRNA expression is also
associated with colon cancer progression, since it is
usually greater in patients being at the initial stages of
the disease or having negative nodal status. BCL2L12
were found also to inhibit post-mitochondrial apoptosis
signaling in glioblastoma.
Cytogenetics
No cytogenetic abnormalities are identified so far.
Hybrid/Mutated gene
Not identified so far.
Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7)
Floros KV, Thomadaki H, Florou D, Talieri M, Scorilas A.
Alterations in mRNA expression of apoptosis-related genes
BCL2, BAX, FAS, caspase-3, and the novel member BCL2L12
after treatment of human leukemic cell line HL60 with the
antineoplastic agent etoposide. Ann N Y Acad Sci. 2006
Dec;1090:89-97
Thomadaki H, Scorilas A. BCL2 family of apoptosis-related
genes: functions and clinical implications in cancer. Crit Rev
Clin Lab Sci. 2006 Jan;43(1):1-67
Thomadaki H, Talieri M, Scorilas A. Treatment of MCF-7 cells
with taxol and etoposide induces distinct alterations in the
expression of apoptosis-related genes BCL2, BCL2L12, BAX,
CASPASE-9 and FAS. Biol Chem. 2006 Aug;387(8):1081-6
Stegh AH, Kim H, Bachoo RM, Forloney KL, Zhang J, et al.
Bcl2L12 inhibits post-mitochondrial apoptosis signaling in
glioblastoma. Genes Dev. 2007 Jan 1;21(1):98-111
Thomadaki H, Scorilas A. Breast cancer cells response to the
antineoplastic agents cisplatin, carboplatin, and doxorubicin at
the mRNA expression levels of distinct apoptosis-related
genes, including the new member, BCL2L12. Ann N Y Acad
Sci. 2007 Jan;1095:35-44
Thomadaki H, Talieri M, Scorilas A. Prognostic value of the
apoptosis related genes BCL2 and BCL2L12 in breast cancer.
Cancer Lett. 2007 Mar 8;247(1):48-55
This article should be referenced as such:
Kontos C, Thomadaki H, Scorilas A. BCL2L12 (BCL2-like 12
(proline-rich)). Atlas Genet Cytogenet Oncol Haematol. 2009;
13(7):467-468.
468