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Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens
Mus musculus
Transcription Factor Encyclopedia  BETA
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No annotation is available in this section for this article. The content below is taken from a related TF, ATF2 (Homo sapiens).

Activating transcription factor 2 (ATF2 or CREB-BP1) is a ubiquitously expressed member of the basic region leucine zipper (bZIP) transcription factor family ATF/CREB which includes other factors such as cyclic-AMP response-element binding protein (CREB), the highly spliced cyclic-AMP response-element modulator protein (CREM) and other members of the ATF family. The family includes 16 cellular stress-responsive transcription factors divided into 6 families on the basis of their sequence similarity:”CREB” (CREB, CREM, ATF-1); “CRE-BP1” (ATF-2, ATFa(ATF-7) ATF-a0, and CRE-BPa); “ATF-3” (ATF-3, ATF-3b, JDP-2); “ATF-4” (ATF-4(CREB-2), “ATF-5”(ATFx); “ATF-6” (ATF6alpha, CREB-RP(ATF6beta)); “B-ATF” (B-ATF, JDP-1)[1][2][3].

The ATF-2 gene is located on human chromosome 2q32 and encodes 505 aa protein. The Family of ATF/CREB plays an important role in mediating cellular homeostasis, stress responses, development and transformation. Studies on ATF2 deficient mice has shown its unique actions during development of skeletal and central nervous system, which cannot be compensated by other members of ATF/CREB family[1].

ATF2 modulates the expression of downstream affected genes by binding as either a homo-dimer or a hetero-dimer with other members of the bZIP family to the cAMP response element (CRE)/ATF consensus binding site 5`-GTGACGT(A/C)(A/G)-3`which is present in many viral and cellular promoters and AP-1 sites within promoter regions of targeted genes.

The native ATF-2 protein in un-stimulated cells stays in an inactive state due to inhibition of the activation domain by binding to its own bZIP domain. ATF-2 trans-activation potential is enhanced by phosphorylation at amino acid residues Thr69 and Thr71 by stress (JNK/SAPK, p38)- or mitogen (MAPK) activated protein kinases and the Ras effector pathways Raf-MEK-ERK and Ral-RalGDS-Src-p38. In vitro ATF-2 can also directly regulate transcription due to its intrinsic histone acetyl transferase (HAT) activity and specific acetylation of Histones H2B and H4. Three residues, AA 296, 297 and 299 have been found to be required for this HAT activity. Interaction with other members of transcriptional machinery can be also dependent on phosphorylation of ATF-2. Interaction of ATF2 with p300/CBP and the basal transcriptional machinery is dependent upon phosphorylation at Ser121 within its p300 interaction domain, mediated by protein kinase C alpha; it has been suggested that Ser121-unphosphorylated ATF2 is transcriptionally silent, necessitating the use of constitutively active ATF2 mutants in transcription studies.

Independent of its transcriptional function ATF2 also plays a role in the DNA damage response whereby it is phosphorylated by ATM on carboxyl terminal residues this results in rapid localisation to ionization radiation induced foci which contain DNA repair proteins and chromatin modifying enzymes. ATF2 is also required for an intact intra S phase checkpoint response to halt DNA replication following DNA damage. No genetic diversities in ATF2 gene have been observed although changes in ATF2 activity and subcellular localisation have been associated with tumour stage and prognosis.

  1. Reimold AM et al. Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice. Nature, 379(6562):262-5. (PMID 8538792)
  2. Nomura N et al. Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1. J. Biol. Chem., 268(6):4259-66. (PMID 8440710)
  1. Vlahopoulos SA et al. The role of ATF-2 in oncogenesis. Bioessays, 30(4):314-27. (PMID 18348191)
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