Dynamic interactions between TIP60 and p300 regulate FOXP3 function through a structural switch defined by a single lysine on TIP60. Cell Rep 2014 Jun 12;7(5):1471-1480
Date
05/20/2014Pubmed ID
24835996Pubmed Central ID
PMC4064594DOI
10.1016/j.celrep.2014.04.021Scopus ID
2-s2.0-84902332541 (requires institutional sign-in at Scopus site) 92 CitationsAbstract
The human FOXP3 molecule is an oligomeric transcriptional factor able to mediate activities that characterize T regulatory cells, a class of lymphocytes central to the regulation of immune responses. The activity of FOXP3 is regulated at the posttranslational level, in part by two histone acetyltransferases (HATs): TIP60 and p300. TIP60 and p300 work cooperatively to regulate FOXP3 activity. Initially, p300 and TIP60 interactions lead to the activation of TIP60 and facilitate acetylation of K327 of TIP60, which functions as a molecular switch to allow TIP60 to change binding partners. Subsequently, p300 is released from this complex, and TIP60 interacts with and acetylates FOXP3. Maximal induction of FOXP3 activities is observed when both p300 and TIP60 are able to undergo cooperative interactions. Conditional knockout of TIP60 in Treg cells significantly decreases the Treg population in the peripheral immune organs, leading to a scurfy-like fatal autoimmune disease.
Author List
Xiao Y, Nagai Y, Deng G, Ohtani T, Zhu Z, Zhou Z, Zhang H, Ji MQ, Lough JW, Samanta A, Hancock WW, Greene MIMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Autoimmune Diseases
E1A-Associated p300 Protein
Forkhead Transcription Factors
HEK293 Cells
Histone Acetyltransferases
Humans
Lysine
Lysine Acetyltransferase 5
Mice
Molecular Sequence Data
Mutation
Protein Binding
T-Lymphocytes, Regulatory
Trans-Activators
