Atlas of Genetics and Cytogenetics in Oncology and Haematology
ATF2 (activating transcription factor 2)
| Identity |
| Other names | CREB1 |
| CRE-BP1 | |
| CREB2 | |
| CREBP1 | |
| HB16 | |
| MGC111558 | |
| TREB7 | |
| Cyclic AMP-dependent transcription factor ATF-2 | |
| cAMP response element-binding protein CRE- BP1 | |
| HGNC (Hugo) | ATF2 |
| Location | 2q31.1 |
| Location_base_pair | Starts at 175647252 and ends at 175741143 bp from pter ( according to hg18-Mar_2006) [Mapping] |
 | |
| DNA/RNA |
 | |
| ATF2 gene structure based on data available in the Ensembl release 44. Upstream non-coding exons (green). Coding exons (pink), 3' untranslated sequence (red). The size of the exons in nucleotides is indicated below each exon. Exon number is indicated within the exon. | |
| Description | Gene size: 115.93Kb. |
| Transcription | Initiation codon located in exon 4. Normal message is 2109 nucleotides. Some alternatively spliced RNA messages have been detected; but they are likely to represent splicing intermediates since no protein has been detected/expressed from these alternative messages in humans. |
| Protein |
| Note | Protein of 505 aminoacids and a size of 52.27 kDa. Functions as a dimer, either homodimer or heterodimer with proteins of the jun family (e.g.: c-Jun, c-Fos). |
 | |
| Localisation | Nuclear protein. |
| Function | Transcription factor which binds to the cAMP-responsive element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'). ATF2 binds DNA as a dimer. The specificity of the DNA target sequence that is recognized by dimers containing ATF2 is different depending on whether it is a homodimer or it forms a heterodimer with another JUN protein. |
| Mutations |
| Note | Lung cancer. |
| Somatic | G to A transition in exon 10. Val258Ile Substitution. |
| Implicated in |
| Entity | Clear Cell Sarcoma |
| Cytogenetics | t(2;12)( q31.1;q13) |
 | |
| The arrow indicates the location of the breakpoint in chromosome 2. The ATF2 gene breaks within intron 6. In the translocation partner EWS the breakpoint occurs in intron 7. The transcript resulting from the hybrid gene fuses exon7 of EWS to exon 7 of ATF2. | |
| Hybrid/Mutated Gene | EWS-ATF2 fusion transcript. |
| Abnormal Protein | The EWS-ATF2 fusion protein retains the ATF2 C-terminal region that contains the bZIP dimerization domain. But the fusion protein has lost the N-terminal domain of ATF2 that is kinase inducible. The N-terminal region of EWS is retained in the fusion protein but has lost both its RNA binding domain and its Zinc-finger Ran binding domain. |
 | |
| Structure of the EWS-ATF2 fusion protein. | |
| Oncogenesis | EWS-ATF2 may define a novel subset of clear cell sarcoma that occurs preferentially in the gastrointestinal tract and presents little or no melanocytic differentiation. |
| External links |
| Bibliography |
| ATF-2 contains a phosphorylation-dependent transcriptional activation domain. |
| Livingstone C, Patel G, Jones N |
| The EMBO journal. 1995 ; 14 (8) : 1785-1797. |
| PMID 7737129 |
| Stability of the ATF2 transcription factor is regulated by phosphorylation and dephosphorylation. |
| Fuchs SY, Tappin I, Ronai Z |
| The Journal of biological chemistry. 2000 ; 275 (17) : 12560-12564. |
| PMID 10777545 |
| Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment. |
| Bhoumik A, Ivanov V, Ronai Z |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2001 ; 7 (2) : 331-342. |
| PMID 11234888 |
| Distinct effects of cAMP and mitogenic signals on CREB-binding protein recruitment impart specificity to target gene activation via CREB. |
| Mayr BM, Canettieri G, Montminy MR |
| Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (19) : 10936-10941. |
| PMID 11535812 |
| Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis. |
| van Dam H, Castellazzi M |
| Oncogene. 2001 ; 20 (19) : 2453-2464. |
| PMID 11402340 |
| Infrequent mutations of the activating transcription factor-2 gene in human lung cancer, neuroblastoma and breast cancer. |
| Woo IS, Kohno T, Inoue K, Ishii S, Yokota J |
| International journal of oncology. 2002 ; 20 (3) : 527-531. |
| PMID 11836564 |
| Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL. |
| Przybylski GK, Dik WA, Wanzeck J, Grabarczyk P, Majunke S, Martin-Subero JI, Siebert R, Dlken G, Ludwig WD, Verhaaf B, van Dongen JJ, Schmidt CA, Langerak AW |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (2) : 201-208. |
| PMID 15668700 |
| EWS-CREB1: a recurrent variant fusion in clear cell sarcoma--association with gastrointestinal location and absence of melanocytic differentiation. |
| Antonescu CR, Nafa K, Segal NH, Dal Cin P, Ladanyi M |
| Clinical cancer research : an official journal of the American Association for Cancer Research. 2006 ; 12 (18) : 5356-5362. |
| PMID 17000668 |
| Mutual regulation of c-Jun and ATF2 by transcriptional activation and subcellular localization. |
| Liu H, Deng X, Shyu YJ, Li JJ, Taparowsky EJ, Hu CD |
| The EMBO journal. 2006 ; 25 (5) : 1058-1069. |
| PMID 16511568 |
| Functional interaction of CREB binding protein (CBP) with nuclear transport proteins and modulation by HDAC inhibitors. |
| Ryan CM, Harries JC, Kindle KB, Collins HM, Heery DM |
| Cell cycle (Georgetown, Tex.). 2006 ; 5 (18) : 2146-2152. |
| PMID 16969114 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 07-2007 | Pedro A Lazo, Ana Sevilla |
| Instituto de Biologia Molecular y Celular del Cancer, CSIC-Universidad de Salamanca, Salamanca, Spain |
| Citation |
| This paper should be referenced as such : |
| Lazo PA, Sevilla A . ATF2 (activating transcription factor 2). Atlas Genet Cytogenet Oncol Haematol. July 2007 . URL : http://AtlasGeneticsOncology.org/Genes/ATF2ID718ch2q31.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Jun 27 16:37:36 CEST 2009 |
For comments and suggestions or contributions, please contact us