ATF5 (activating transcription factor 5)
2010-06-01 Arthur KK Ching , Nathalie Wong AffiliationDepartment of Anatomical, Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong
Identity
HGNC
LOCATION
19q13.33
IMAGE
LEGEND
Mapping diagram. Base on Human Mar. 2006 (NCBI36/hg18) Assembly.
LOCUSID
ALIAS
ATFX,HMFN0395
FUSION GENES
DNA/RNA
DNA structure diagram. Relative size of the 4 exons of ATF5. Exon 1 and 2 are untranslated exons (NCBI reference sequence NM_012068.4). Blue area is non-coding region and pink is coding region.
Description
The ATF5 gene spans a total genomic size of 5219 bases and is composed of four exons.
Transcription
The human ATF5 transcript is 2268 bp in size (NM_012068.4) and contains 4 exons. Exon 1 and 2 are non-coding exons and the size of open reading frame is 849 bp.
Proteins
Protein structure diagram.
Description
ATF5 consists of 282 amino acid with MW of 30.69 kDa (NCBI reference sequence NP_036200.2).
Expression
Northern blot analysis revealed ubiquitous expression of ATF5, with highest levels in liver, lung, adipose tissue, heart, and skeletal muscle.
Localisation
Nucleus and cytoplasm.
Function
ATF5 is a member of basic-region leucine zipper (bZIP) proteins family which binds the cAMP response element (CRE) consensus sequence: 5GTGACGT(C/A)(G/A). This sequence is present in many viral and cellular promoters. ATF within or between subgroups can form homo- or hetero-dimer through the bZIP domain and the dimer can then bind to the DNA through the basic-motif and function as a transcription factor. Recently, another novel ATF5 consensus DNA binding sequence (CYTCTYCCTTW) was found in C6 glioma and MCF7 using a cyclic amplification and selection of targets (CASTing) approach (Li et al., 2009).
ATF5 is linked to many cellular function including cell cycle progression, metabolite homeostasis (Al Sarraj et al., 2005; Watatani et al., 2007), cellular differentiation and apoptosis. It involves in the proliferation and differentiation of neural cells (Angelastro et al., 2003; Angelastro et al., 2005; Mason et al., 2005) and has been shown to take part in the skeletal development of mouse limb (Shinomura et al., 2006; Satake at al., 2009). Data from various groups also suggested that ATF5 can function as anti-apoptotic factor (Devireddy et al., 2001; Persengiev et al., 2002; Nishioka et al., 2009).
Coimmunoprecipitation and GST pull-down analyses confirmed the association of the C-terminal bZIP motif of ATF5 with the PRL-1 PTPase domain and adjacent residues of PTP4A1 in vitro. SDS-PAGE analysis showed that PRL-1 dephosphorylates ATF5 in vitro (Peters et al., 2001).
ATF5 has been shown to interact with various proteins including Cyclin D3 (Liu et al., 2004), GABAB receptors (White et al., 2000), HTLV-1 viral protein Tax (Forgacs et al., 2005), E2 ubiguitin-conjugating enzyme Cdc34, PRL-1 and DISC1 (Morris et al., 2003; Fujii et al., 2007; Tomppo et al., 2009). It is a target of Cdc34-dependent ubiquitin-mediated proteolysis (Pati et al., 1999). Study indicates that during stress condition, eIF2 is phosphorylated and subsequently direct ATF5 translation in cell (Watatani et al., 2008; Zhou et al., 2008). Recent study of the promoter of ATF5 also suggested that its transcription is regulated by EBF1 (Wei et al., 2010).
ATF5 is linked to many cellular function including cell cycle progression, metabolite homeostasis (Al Sarraj et al., 2005; Watatani et al., 2007), cellular differentiation and apoptosis. It involves in the proliferation and differentiation of neural cells (Angelastro et al., 2003; Angelastro et al., 2005; Mason et al., 2005) and has been shown to take part in the skeletal development of mouse limb (Shinomura et al., 2006; Satake at al., 2009). Data from various groups also suggested that ATF5 can function as anti-apoptotic factor (Devireddy et al., 2001; Persengiev et al., 2002; Nishioka et al., 2009).
Coimmunoprecipitation and GST pull-down analyses confirmed the association of the C-terminal bZIP motif of ATF5 with the PRL-1 PTPase domain and adjacent residues of PTP4A1 in vitro. SDS-PAGE analysis showed that PRL-1 dephosphorylates ATF5 in vitro (Peters et al., 2001).
ATF5 has been shown to interact with various proteins including Cyclin D3 (Liu et al., 2004), GABAB receptors (White et al., 2000), HTLV-1 viral protein Tax (Forgacs et al., 2005), E2 ubiguitin-conjugating enzyme Cdc34, PRL-1 and DISC1 (Morris et al., 2003; Fujii et al., 2007; Tomppo et al., 2009). It is a target of Cdc34-dependent ubiquitin-mediated proteolysis (Pati et al., 1999). Study indicates that during stress condition, eIF2 is phosphorylated and subsequently direct ATF5 translation in cell (Watatani et al., 2008; Zhou et al., 2008). Recent study of the promoter of ATF5 also suggested that its transcription is regulated by EBF1 (Wei et al., 2010).
Homology
ATF5 gene is highly conserved in mammals. Protein identity percentage of human ATF5 compared with chimpanzee, cow, mouse, and rat is 98.9, 88.0, 87.5 and 88.9 respectively.
Mutations
Germinal
Unknown.
Somatic
Exon2 Leu141Phe, Exon2 Val257Met and Exon2 Arg275Trp.
Implicated in
Entity name
Various cancers
Note
ATF5 is showed to be overexpressed in various cancers by TMA (tissue microarray) that includes breast cancer, glioblastomas, adenocarcinomas, transitional cell carcinomas, squamous cell carcinomas and metastatic carcinomas of various origin (Monaco et al., 2007). However, in hepatocellular carcinoma, ATF5 expression is down-regulated, suggesting that role of ATF5 in tumor is highly depending on the tumor type.
Entity name
Glioma
Note
ATF5 has been shown to be highly expressed in perinecrotic palisades, the most aggressive forms of malignant gliomas. In a study of 28 tumors without perinecrotic palisades, the level of ATF5 expression together with 4 other genes, negatively correlated with time of patient survival. Interference of ATF5 expression in glioma cell lines causes apoptosis but not in cultured astrocytes. These findings suggested that ATF5 plays a role in maintaining cell survival in glioma.
Cytogenetics
Unknown.
Hybrid gene
Unknown.
Fusion protein
Unknown.
Entity name
Hepatocellular carcinoma
Note
A study has showed that ATF5 is down-regulated in 60 out of 77 cases in HCC, as in contrast to adult normal liver where expression of ATF5 is particularly high. Gene expression profiling was also done by ectopic re-expression of ATF5 suggesting cell cycle, actin skeleton regulation, MAPK signaling and focal adhesion are the pathways modulated by ATF5. These findings suggested that ATF5 down regulation may contribute to the development of HCC. The inactivation mechanisms of ATF5 involve epigenetic silencing and chromosome copy number loss.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16164412 | 2005 | Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP. | Al Sarraj J et al |
| 16170340 | 2006 | Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. | Angelastro JM et al |
| 16116475 | 2006 | Identification of RASSF1A modulated genes in nasopharyngeal carcinoma. | Chow LS et al |
| 11486081 | 2001 | Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation. | Devireddy LR et al |
| 16254489 | 2005 | Histology-based expression profiling yields novel prognostic markers in human glioblastoma. | Dong S et al |
| 15890932 | 2005 | The bZIP transcription factor ATFx binds human T-cell leukemia virus type 1 (HTLV-1) Tax and represses HTLV-1 long terminal repeat-mediated transcription. | Forgacs E et al |
| 18701499 | 2008 | Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest. | Gho JW et al |
| 19046351 | 2009 | The transcription factor ATF5: role in neurodevelopment and neural tumors. | Greene LA et al |
| 19531563 | 2009 | Identification of a novel DNA binding site and a transcriptional target for activating transcription factor 5 in c6 glioma and mcf-7 breast cancer cells. | Li G et al |
| 15358120 | 2004 | Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity. | Liu W et al |
| 15950153 | 2005 | ATF5 regulates the proliferation and differentiation of oligodendrocytes. | Mason JL et al |
| 17266024 | 2007 | The transcription factor ATF5 is widely expressed in carcinomas, and interference with its function selectively kills neoplastic, but not nontransformed, breast cell lines. | Monaco SE et al |
| 12812986 | 2003 | DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. | Morris JA et al |
| 10373550 | 1999 | Human Cdc34 and Rad6B ubiquitin-conjugating enzymes target repressors of cyclic AMP-induced transcription for proteolysis. | Pati D et al |
| 12130540 | 2002 | Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors. | Persengiev SP et al |
| 11278933 | 2001 | ATF-7, a novel bZIP protein, interacts with the PRL-1 protein-tyrosine phosphatase. | Peters CS et al |
| 19712269 | 2009 | Spatio-temporal expression of activating transcription factor 5 in the skeletal development of mouse limb. | Satake H et al |
| 19251251 | 2009 | Association between genes of Disrupted in schizophrenia 1 (DISC1) interactors and schizophrenia supports the role of the DISC1 pathway in the etiology of major mental illnesses. | Tomppo L et al |
| 18055463 | 2008 | Stress-induced translation of ATF5 mRNA is regulated by the 5'-untranslated region. | Watatani Y et al |
| 20423929 | 2010 | Identification and characterization of the promoter of human ATF5 gene. | Wei Y et al |
| 11087824 | 2000 | The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx. | White JH et al |
| 18195013 | 2008 | Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions. | Zhou D et al |
Other Information
Locus ID:
NCBI: 22809
MIM: 606398
HGNC: 790
Ensembl: ENSG00000169136
Variants:
dbSNP: 22809
ClinVar: 22809
TCGA: ENSG00000169136
COSMIC: ATF5
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38472656 | 2024 | The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy. | 0 |
| 38472656 | 2024 | The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy. | 0 |
| 35939173 | 2023 | ATF5 Attenuates Apoptosis in Hippocampal Neurons with Seizures Evoked by Mg(2+)-Free Medium via Regulating Mitochondrial Unfolded Protein Response. | 2 |
| 38014922 | 2023 | Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance. | 1 |
| 38223508 | 2023 | ATF5 promotes malignant T cell survival through the PI3K/AKT/mTOR pathway in cutaneous T cell lymphoma. | 1 |
| 35939173 | 2023 | ATF5 Attenuates Apoptosis in Hippocampal Neurons with Seizures Evoked by Mg(2+)-Free Medium via Regulating Mitochondrial Unfolded Protein Response. | 2 |
| 38014922 | 2023 | Activating Transcription Factor 5 Promotes Neuroblastoma Metastasis by Inducing Anoikis Resistance. | 1 |
| 38223508 | 2023 | ATF5 promotes malignant T cell survival through the PI3K/AKT/mTOR pathway in cutaneous T cell lymphoma. | 1 |
| 33640883 | 2021 | Maf1 suppression of ATF5-dependent mitochondrial unfolded protein response contributes to rapamycin-induced radio-sensitivity in lung cancer cell line A549. | 7 |
| 33959786 | 2021 | Influence of genetic variants in asparaginase pathway on the susceptibility to asparaginase-related toxicity and patients' outcome in childhood acute lymphoblastic leukemia. | 4 |
| 33980247 | 2021 | ATF5 and HIF1α cooperatively activate HIF1 signaling pathway in esophageal cancer. | 5 |
| 34262025 | 2021 | ATF5, a putative therapeutic target for the mitochondrial DNA 3243A > G mutation-related disease. | 10 |
| 34617722 | 2021 | Human Cytomegalovirus Infection Activates Glioma Activating Transcription Factor 5 via microRNA in a Stress-Induced Manner. | 8 |
| 33640883 | 2021 | Maf1 suppression of ATF5-dependent mitochondrial unfolded protein response contributes to rapamycin-induced radio-sensitivity in lung cancer cell line A549. | 7 |
| 33959786 | 2021 | Influence of genetic variants in asparaginase pathway on the susceptibility to asparaginase-related toxicity and patients' outcome in childhood acute lymphoblastic leukemia. | 4 |
Citation
Arthur KK Ching ; Nathalie Wong
ATF5 (activating transcription factor 5)
Atlas Genet Cytogenet Oncol Haematol. 2010-06-01
Online version: http://atlasgeneticsoncology.org/gene/50361/atf5
