EKLF/KLF1 is ubiquitinated in vivo and its stability is regulated by activation domain sequences through the 26S proteasome.
Erythroid Krüppel-like factor (EKLF/KLF1) is an erythroid specific, C(2)H(2) zinc finger transcription factor that is essential for the proper chromatin structure and expression of the adult beta-globin gene. Herein, we determine that 26S proteasome inhibitors lead to an accumulation of EKLF protein in murine erythroleukemia (MEL) cells. In addition, EKLF half-life in both MEL cells (<3h) and fetal liver cells (between 6 and 9h) is stabilized in the presence of these inhibitors. EKLF is ubiquitinated in vivo, however its modification does not rely on a particular internal lysine. Finally, EKLF contains two PEST sequences within its N-terminus that have no effect on the ability of EKLF to be ubiquitinated but contribute to its destabilization.
Quadrini
Karen J
KJ
The Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Bieker
James J
JJ
D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism; D005333:Fetus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005914:Globins / Q000096:biosynthesis; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D051741:Kruppel-Like Transcription Factors; D025801:Ubiquitin; C080774:erythroid Kruppel-like factor; D005914:Globins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D008239:Lysine