EKLF/KLF1 is ubiquitinated in vivo and its stability is regulated by activation domain sequences through the 26S proteasome.

Abstract

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.

• Authors: Karen J Quadrini, James J Bieker
• Journal: FEBS letters (FEBS Lett) Vol. 580 Issue 9 Pg. 2285-93 (Apr 17 2006) ISSN: 0014-5793 [Print] England
• PMID: 16579989 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Chromatin
• Kruppel-Like Transcription Factors
• Ubiquitin
• erythroid Kruppel-like factor
• Globins
• Proteasome Endopeptidase Complex
• ATP dependent 26S protease
• Lysine

Topics

• Amino Acid Motifs (genetics)
• Animals
• COS Cells
• Chlorocebus aethiops
• Chromatin (metabolism)
• Fetus (metabolism)
• Gene Expression Regulation, Developmental (physiology)
• Globins (biosynthesis)
• Humans
• Kruppel-Like Transcription Factors (genetics, metabolism)
• Liver (metabolism)
• Lysine (genetics, metabolism)
• Mice
• Proteasome Endopeptidase Complex (metabolism)
• Protein Processing, Post-Translational (physiology)
• Ubiquitin (genetics, metabolism)