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| Description | The EP400 protein (isoform 2) is 3124 amino acids long and its molecular weight is about 400 kDa. It was cloned and characterized in 2001 thanks to its interation with the E1A oncoprotein.
Isoform 1 produces a 3160 aa long protein. Isoform 3 produces a 3087 aa long protein. Isoform 4 produces a 3043 aa long protein.
There has been no experimental confirmation for isoforms 3 and 4.
The only described post-translational modification is a phosphorylation on Ser736. |
| Expression | No data. |
| Localisation | EP400 belongs to chromatin remodelling complexes which are located in the nucleus, so it is probably nuclear. However, its cellular localization has not been formally monitored to date. |
| Function | EP400 belongs to the SWI2/SNF2 family of ATPases and is found in two highly related chromatin remodelling complexes : the Tip60 and p400 complexes. In these complexes, EP400 is associated with other enzymes such as the Tip60 histone acetyltransferase and/or the RuvBL1 and RuvBL2 helicases. (Note : putative specific functions of each splicing variant have not been investigated to date) Functions at the cellular level :
EP400 has been implicated in cell cycle control, apoptosis and development.
First, the depletion of EP400 in untransformed human fibroblasts leads to senescence through induction of the p53-p21 pathway. Likewise, the EP400 knock-down induces a p21-dependent cell cycle arrest in human cell lines. According to these results, EP400 seems to favour cell proliferation.
On the other hand, EP400 is required for E1A-mediated apoptosis. Similarly, EP400 is required for apoptosis upon DNA damage in human cell lines. Thus, EP400 also favours apoptosis, possibly through preventing cell cycle arrest.
Finally, the murine homolog of EP400 appears to be involved in embryonic hematopoiesis. Functions at the molecular level :
EP400 has ATP-dependent chromatin remodelling activity. Accordingly, EP400 was shown to be recruited along with the Tip60 complex on promoters by the c-myc and E2F transcription factors. Moreover, the EP400 homolog in drosophila is able to exchange specific histone variants at double-strand breaks. |
| Homology | EP400 contains the SNF2 N-terminal domain shared by all ATPases of the SWI2/SNF2 family (SNF2, STH1, RAD16, RAD54, ISWI...). It also bears helicase-specific domains (see diagram):
an helicase C-terminal domain an HSA domain a DEXH box which contains the ATP-binding region. Putative homologs in other species (non exhaustive) :
M.musculus : Ep400 R.norvegicus : Ep400 G.gallus : EP400 D.melanogaster : DOM or domino |
| The p400 complex is an essential E1A transformation target. |
| Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM |
| Cell. 2001 ; 106 (3) : 297-307. |
| PMID 11509179 |
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| MYC recruits the TIP60 histone acetyltransferase complex to chromatin. |
| Frank SR, Parisi T, Taubert S, Fernandez P, Fuchs M, Chan HM, Livingston DM, Amati B |
| EMBO reports. 2003 ; 4 (6) : 575-580. |
| PMID 12776177 |
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| Large-scale characterization of HeLa cell nuclear phosphoproteins. |
| Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villˆ©n J, Li J, Cohn MA, Cantley LC, Gygi SP |
| Proceedings of the National Academy of Sciences of the United States of America. 2004 ; 101 (33) : 12130-12135. |
| PMID 15302935 |
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| Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. |
| Kusch T, Florens L, Macdonald WH, Swanson SK, Glaser RL, Yates JR 3rd, Abmayr SM, Washburn MP, Workman JL |
| Science (New York, N.Y.). 2004 ; 306 (5704) : 2084-2087. |
| PMID 15528408 |
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| The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway. |
| Chan HM, Narita M, Lowe SW, Livingston DM |
| Genes & development. 2005 ; 19 (2) : 196-201. |
| PMID 15655109 |
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| p400 is required for E1A to promote apoptosis. |
| Samuelson AV, Narita M, Chan HM, Jin J, de Stanchina E, McCurrach ME, Narita M, Fuchs M, Livingston DM, Lowe SW |
| The Journal of biological chemistry. 2005 ; 280 (23) : 21915-21923. |
| PMID 15741165 |
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| Tip60 and p400 are both required for UV-induced apoptosis but play antagonistic roles in cell cycle progression. |
| Tyteca S, Vandromme M, Legube G, Chevillard-Briet M, Trouche D |
| The EMBO journal. 2006 ; 25 (8) : 1680-1689. |
| PMID 16601686 |
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| p400 function is required for the adenovirus E1A-mediated suppression of EGFR and tumour cell killing. |
| Flinterman MB, Mymryk JS, Klanrit P, Yousef AF, Lowe SW, Caldas C, Gˆ§ken J, Farzaneh F, Tavassoli M |
| Oncogene. 2007 ; 26 (48) : 6863-6874. |
| PMID 17486071 |
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| Critical role of the p400/mDomino chromatin-remodeling ATPase in embryonic hematopoiesis. |
| Ueda T, Watanabe-Fukunaga R, Ogawa H, Fukuyama H, Higashi Y, Nagata S, Fukunaga R |
| Genes to cells : devoted to molecular & cellular mechanisms. 2007 ; 12 (5) : 581-592. |
| PMID 17535249 |
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