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

Karen J. Quadrini; James J. Bieker

doi:10.1016/j.febslet.2006.03.039

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

Karen J. Quadrini
, James J. Bieker

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Erythroid Krüppel-like factor (EKLF/KLF1) is an erythroid specific, C₂H₂ zinc finger transcription factor that is essential for the proper chromatin structure and expression of the adult β-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 (<3 h) and fetal liver cells (between 6 and 9 h) 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.

Original language	English
Pages (from-to)	2285-2293
Number of pages	9
Journal	FEBS Letters
Volume	580
Issue number	9
DOIs	https://doi.org/10.1016/j.febslet.2006.03.039
State	Published - 17 Apr 2006

Keywords

Erythroid cells
PEST sequence
Transcription factor
Ubiquitin
Zinc finger protein

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10.1016/j.febslet.2006.03.039

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@article{47d7b91386444ee3bc9b215002a86ff4,

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

abstract = "Erythroid Kr{\"u}ppel-like factor (EKLF/KLF1) is an erythroid specific, C2H2 zinc finger transcription factor that is essential for the proper chromatin structure and expression of the adult β-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 (<3 h) and fetal liver cells (between 6 and 9 h) 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.",

keywords = "Erythroid cells, PEST sequence, Transcription factor, Ubiquitin, Zinc finger protein",

author = "Quadrini, \{Karen J.\} and Bieker, \{James J.\}",

note = "Funding Information: We thank Zhen-qiang Pan for the HA-tagged ubiquitin expression plasmid and Dora Dias for the in vivo ubiquitination assay protocol and technical advice. We also thank Sherman Wilk for technical advice and members of the Bieker lab for discussion throughout the course of the work. This work was supported by NIH PHS Grants T32 GM08553 (to K.J.Q.) and R01 DK46865 (to J.J.B.). ",

year = "2006",

month = apr,

day = "17",

doi = "10.1016/j.febslet.2006.03.039",

language = "English",

volume = "580",

pages = "2285--2293",

journal = "FEBS Letters",

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T1 - EKLF/KLF1 is ubiquitinated in vivo and its stability is regulated by activation domain sequences through the 26S proteasome

AU - Quadrini, Karen J.

AU - Bieker, James J.

N1 - Funding Information: We thank Zhen-qiang Pan for the HA-tagged ubiquitin expression plasmid and Dora Dias for the in vivo ubiquitination assay protocol and technical advice. We also thank Sherman Wilk for technical advice and members of the Bieker lab for discussion throughout the course of the work. This work was supported by NIH PHS Grants T32 GM08553 (to K.J.Q.) and R01 DK46865 (to J.J.B.).

PY - 2006/4/17

Y1 - 2006/4/17

N2 - Erythroid Krüppel-like factor (EKLF/KLF1) is an erythroid specific, C2H2 zinc finger transcription factor that is essential for the proper chromatin structure and expression of the adult β-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 (<3 h) and fetal liver cells (between 6 and 9 h) 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.

AB - Erythroid Krüppel-like factor (EKLF/KLF1) is an erythroid specific, C2H2 zinc finger transcription factor that is essential for the proper chromatin structure and expression of the adult β-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 (<3 h) and fetal liver cells (between 6 and 9 h) 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.

KW - Erythroid cells

KW - PEST sequence

KW - Transcription factor

KW - Ubiquitin

KW - Zinc finger protein

UR - https://www.scopus.com/pages/publications/33646010066

U2 - 10.1016/j.febslet.2006.03.039

DO - 10.1016/j.febslet.2006.03.039

M3 - Article

C2 - 16579989

AN - SCOPUS:33646010066

SN - 0014-5793

VL - 580

SP - 2285

EP - 2293

JO - FEBS Letters

JF - FEBS Letters

IS - 9

ER -

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

Abstract

Keywords

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