[Prothyomosin alpha interaction with KEAP1 doesn't lead to prothymosin alpha ubiquination and degradation].
Prothymosin alpha (ProTalpha) is a highly conserved protein in vertebrates that possesses a number of biological functions. One of these functions of ProTalpha is the ability to enhance antioxidant defence system of a cell via its interaction with Keap1 protein. Keap1 is a repressor of Nrf2, a transcription factor responsible for activation of genes that code for defensive proteins. While bound to Nrf2, Keap1 exports Nrf2 from the nucleus to the cytoplasm and, being adaptor protein for ubiquitin ligase, promotes ubiquitination of Nrf2 and its subsequent degradation by 26S proteasome. ProTalpha and Nrf2 compete for interaction with Keap1, therefore ProTalpha is able to liberate Nrf2 from complex with Keap1 and hence contribute to Nrf2-dependent transcription. Here we were interested in elucidating possible consequences for ProTalpha of its interaction with Keap1. We have shown that, despite ProTalpha interaction with Keap1, ProTalpha is a stable protein. In contrast to Nrf2 ProTalpha was not subjected to Keap-dependent ubiquitination, degradation and export from the nucleus. Furthermore, ubiquitination of ProTalpha was undetectable even when Keap1 and ubiquitin were overexpressed. It appears that ProTalpha contribution to Nrf2-dependent transcription is accomplished via the increase of free Nrf2 rather then the increase of total intracellular amount of Nrf2.
Mel'nikov
S V
SV
Evstaf'eva
A G
AG
Vartapetian
A B
AB
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D011498:Protein Precursors; D025801:Ubiquitin; C040782:prothymosin alpha; D013947:Thymosin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease