FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity.
Forkhead box protein P3 (FOXP3) contributes to a unique transcriptional signature and serves as a functional marker of CD4(+)CD25(+) natural regulatory T cells. Dysfunction of FOXP3 in human is associated with fatal autoimmune disease known as immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) or X-linked autoimmunity-allergic disregulation syndrome (XLAAD). FOXP3 also can act as a breast tumor suppressor of the v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (neuro/glioblastoma derived oncogene homolog (avian)) (Her2/neu) gene. While the suppressive functions of FOXP3 in maintaining the immune balance between tolerance and autoimmunity are obvious, the underlying molecular mechanism remains almost entirely undefined. Recent studies indicate that FOXP3 may form a dynamic superamolecular complex with a variety of molecular partners including transcription factors and enzymatic proteins to regulate transcription. How the FOXP3 ensemble changes in response to T-cell receptor signals and/or proinflammatory signal remains unclear although work from this laboratory has revealed its complexity. Structural information on FOXP3 complex may offer novel functional insights, as well as facilitate the development of rational means to modulate regulatory T-cell function in various human diseases.
Zhou
Zhaocai
Z
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, 19104-6082, USA.
Song
Xiaomin
X
Li
Bin
B
Greene
Mark I
MI
D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism* / Q000502:physiology*; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D050778:NFATC Transcription Factors / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D050676:Core Binding Factor Alpha 2 Subunit; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050778:NFATC Transcription Factors; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D018808:Transcription Factor AP-1; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C543273:HDAC7 protein, human; D006655:Histone Deacetylases