Department of Health Science, Medical Genetics, Universita degli Studi di Milano, Milano, Italy
p300 has also some more indirect chromatin-related roles:
4) DNA replication and repair: p300 interacts with various replication and repair proteins, including proliferating cell nuclear antigen (PCNA), the Recq4 helicase, Flap endonuclease 1 (Fen1), DNA polymerase b and thymine DNA glycosylase, with the latter three also serving as acetylation substrates.
5) Cell cycle regulation: p300 associates with the complex formed between cyclin E and cyclin-dependent kinase 2 (cdk2) regulating proper progression of the cell cycle.
6) p53 activity regulation: p300 is involved in p53 degradation, which depends on the murine double minute 2 protein (MDM2). Degradation and ubiquitination of p53 is dependent on MDM2, and a ternary complex between these two proteins and p300 regulates the turnover of p53 itself in cycling cells. Furthermore, the CH-1 region of p300 displays polyubiquitin ligase activity towards p53, and could therefore play a key role in controlling p53 levels.
7) Nuclear import: p300 can acetylate two proteins involved in regulating nuclear import, the importin-α1 isoform Rch1 and importin-α7, and could therefore play a role in this process.
Because of its ability of interacting with more than 400 partner proteins, p300 can be considered a "hub" (Bedford et al., 2014). Its interactome includes pro-proliferative proteins and oncoproteins: c-Myc, c-Myb, CREB, c-Jun and c-Fos; transforming viral proteins: E1A, and E6; as well as tumor suppressors and pro-apoptotic proteins: Forkhead box class O (FoxO) transcription factors FoxO1, FoxO3a, and FoxO4, signal transducers and activators of transcription (STAT) 1 and STAT 2, Hypoxia-inducible factor 1α (HIF-1α), breast cancer 1 (BRCA1), SMA/MAD homology (Smad) proteins, the Runt-related transcription factor (RUNX), E2 Transcription Factor (E2F), and E-proteins (Wang et al., 2013).
Gloria Negri ; Cristina Gervasini
EP300 (E1A binding protein p300)
Atlas Genet Cytogenet Oncol Haematol. 2014-11-01
Online version: http://atlasgeneticsoncology.org/gene/97/p300id97
2000-01-01 EP300 (E1A binding protein p300) by Jean-Loup Huret