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Gene Section Mini Review Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Mini Review 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 Identity sequences. Other names: BPR; MGC120313; MGC120314; BCL2L12 protein also includes various putative MGC120315 posttranslational modification sites. There are HGNC (Hugo): BCL2L12 numerous potential sites for O-glycosylation. Furthermore, several possible sites of phosphorylation Location: 19q13.3 have been identified for cAMP-dependent protein Local order: Telomere to centromere. kinase, protein kinase C, and casein kinase 2. In addition, several N-myristoylation sites have been DNA/RNA predicted. The BCL2L12 protein was found to have proline-rich sites. One PPPP site as well as five PP Description amino acid sites are present in this protein. Eight Spanning 8.8 kb of genomic DNA, the BCL2L12 gene putative PXXP motifs were also identified. Proline-rich consists of 6 introns and 7 exons. motifs are characterized by the presence of the Transcription consensus PXXP tetrapeptide, found in all proline-rich proteins identified to date. It is known that SH3 The BCL2L12 gene has three splice variants with domains recognize proline-rich sequences and that all differences in exon 3. The predominant form is 1855 bp known SH3-binding proteins contain proline-rich and encodes the full-length protein. The second splice regions with at least one PXXP motif. Proline-rich variant lacks exon 3, which consists of 143 bp, thus domains have been identified in a number of diverse resulting in no ORF. The third splice variant lacks 3 bp proteins such as epidermal growth factors, at the beginning of exon 3 and encodes a protein having phosphatidylinositol 3-kinase, and, more recently, the one amino acid residue less than the full-lengh protein. small GTPase RRAS protein and members of the Pseudogene RRAS superfamily such as the TC21 protein. Moreover, the amino acid loop (PPSPEP) at positions Not identified so far. 271-276 of the BCL2L12 protein is identical with the PXXP motif present in the RRAS and TC21 Protein oncogenes. This motif is required for integrin Description activation. The splice variant BCL2L12-A is expected to encode a The BCL2L12 protein is composed of 334 amino acids, truncated protein of 176 amino acids with five PP with a calculated molecular mass of 36.8 kDa and an proline sites, two putative PXXP motifs, and no BH2 isoelectric point of 9.45. The BCL2L12 protein homology domain. 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 Scorilas A, Kyriakopoulou L, Yousef GM, Ashworth LK, in glandular epithelia in various organs, such as Kwamie A, Diamandis EP. Molecular cloning, physical gastrointestinal tract and/or breast. Lower BCL2L12 mapping, and expression analysis of a novel gene, BCL2L12, protein expression has been found in prostate tissue. encoding a proline-rich protein with a highly conserved BH2 domain of the Bcl-2 family. Genomics. 2001 Mar 1;72(2):217- Function 21 BCL2L12 is involved in apoptosis. However, its Floros KV, Thomadaki H, Lallas G, Katsaros N, Talieri M, proapoptotic or antiapoptotic role in different types of Scorilas A. Cisplatin-induced apoptosis in HL-60 human cells and conditions remains unclear. promyelocytic leukemia cells: differential expression of BCL2 and novel apoptosis-related gene BCL2L12. Ann N Y Acad Homology Sci. 2003 Dec;1010:153-8 Human BCL2L12 shares 98% and 96% identity with Talieri M, Diamandis EP, Katsaros N, Gourgiotis D, Scorilas A. chimpanzee and Rhesus monkey Bcl2l12, respectively, Expression of BCL2L12, a new member of apoptosis-related genes, in breast tumors. Thromb Haemost. 2003 and 83% identity with rat/mouse Bc2l12 as well. Jun;89(6):1081-8 Floros KV, Thomadaki H, Katsaros N, Talieri M, Scorilas A. Mutations mRNA expression analysis of a variety of apoptosis-related genes, including the novel gene of the BCL2-family, BCL2L12, Note in HL-60 leukemia cells after treatment with carboplatin and No germinal or somatic mutations are identified to be doxorubicin. Biol Chem. 2004 Nov;385(11):1099-103 associated with cancer so far. Mathioudaki K, Scorilas A, Papadokostopoulou A, Xynopoulos D, Arnogianaki N, Agnanti N, Talieri M. Expression analysis of Implicated in BCL2L12, a new member of apoptosis-related genes, in colon cancer. Biol Chem. 2004 Sep;385(9):779-83 Human Leukemias, Solid Tumors Floros KV, Talieri M, Scorilas A. Topotecan and methotrexate Note alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells. Biol Chem. 2006 Significant alterations of BCL2L12 mRNA expression Dec;387(12):1629-33 have been noticed in HL-60 leukemia cells as well as in MCF7 breast cancer cells, after treatment with various Floros KV, Thomadaki H, Florou D, Talieri M, Scorilas A. Alterations in mRNA expression of apoptosis-related genes antineoplastic agents including cisplatin, carboplatin, BCL2, BAX, FAS, caspase-3, and the novel member BCL2L12 doxorubicin, methotrexate, and etoposide. These after treatment of human leukemic cell line HL60 with the important modulations of BCL2L12 mRNA levels antineoplastic agent etoposide. Ann N Y Acad Sci. 2006 seem to depend on both the apoptotic inducer and the Dec;1090:89-97 specific apoptotic pathway, implying a strong Thomadaki H, Scorilas A. BCL2 family of apoptosis-related relationship between alterations in BCL2L12 mRNA genes: functions and clinical implications in cancer. Crit Rev levels and apoptosis. Clin Lab Sci. 2006 Jan;43(1):1-67 Expression analysis of the BCL2L12 gene has showed Thomadaki H, Talieri M, Scorilas A. Treatment of MCF-7 cells that BCL2L12 mRNA expression may be considered as with taxol and etoposide induces distinct alterations in the expression of apoptosis-related genes BCL2, BCL2L12, BAX, a new prognostic marker for breast cancer, as breast CASPASE-9 and FAS. Biol Chem. 2006 Aug;387(8):1081-6 tumours of lower stage or grade are more often BCL2L12-positive. Moreover, breast cancer patients Stegh AH, Kim H, Bachoo RM, Forloney KL, Zhang J, et al. Bcl2L12 inhibits post-mitochondrial apoptosis signaling in with BCL2L12 mRNA expression are less likely to glioblastoma. Genes Dev. 2007 Jan 1;21(1):98-111 relapse or die, in comparison with BCL2L12-negative Thomadaki H, Scorilas A. Breast cancer cells response to the patients. Regarding BCL2L12 gene expression in colon antineoplastic agents cisplatin, carboplatin, and doxorubicin at cancer, the BCL2L12-A transcript is overexpressed in the mRNA expression levels of distinct apoptosis-related cancer tissues as compared to their normal mucosa genes, including the new member, BCL2L12. Ann N Y Acad counterparts. BCL2L12-A mRNA expression is also Sci. 2007 Jan;1095:35-44 associated with colon cancer progression, since it is Thomadaki H, Talieri M, Scorilas A. Prognostic value of the usually greater in patients being at the initial stages of apoptosis related genes BCL2 and BCL2L12 in breast cancer. the disease or having negative nodal status. BCL2L12 Cancer Lett. 2007 Mar 8;247(1):48-55 were found also to inhibit post-mitochondrial apoptosis This article should be referenced as such: signaling in glioblastoma. Kontos C, Thomadaki H, Scorilas A. BCL2L12 (BCL2-like 12 Cytogenetics (proline-rich)). Atlas Genet Cytogenet Oncol Haematol. 2009; No cytogenetic abnormalities are identified so far. 13(7):467-468. Hybrid/Mutated gene Not identified so far. Atlas Genet Cytogenet Oncol Haematol. 2009; 13(7) 468 .
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