KLF6 degradation after apoptotic DNA damage

Michaela S. Banck; Simon W. Beaven; Goutham Narla; Martin J. Walsh; Scott L. Friedman; Andreas S. Beutler

doi:10.1016/j.febslet.2006.10.077

KLF6 degradation after apoptotic DNA damage

Michaela S. Banck, Simon W. Beaven, Goutham Narla, Martin J. Walsh, Scott L. Friedman, Andreas S. Beutler

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

27 Scopus citations

Abstract

Krüppel-like factor 6 (KLF6) is a cancer gene (www.sanger.ac.uk/genetics/CGP/Census/). Here, we demonstrate that KLF6 protein is rapidly degraded when apoptosis is induced via the intrinsic pathway by cisplatin, adriamycin, or UVB irradiation in multiple cell lines (HCT116, SW40, HepG2, PC3-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR-90). KLF6 degradation occurred in the presence or absence of p53, was associated with ubiquitination, mediated by the proteasome (half-life 16 min, unstimulated), and independent of caspases and calpain. KLF6 was unchanged by apoptosis via the extrinsic/death-receptor pathway. Deregulation of KLF6 stability may alter its tumor suppressor function and/or the response of tumors to chemotherapeutics.

Original language	English
Pages (from-to)	6981-6986
Number of pages	6
Journal	FEBS Letters
Volume	580
Issue number	30
DOIs	https://doi.org/10.1016/j.febslet.2006.10.077
State	Published - 22 Dec 2006

Keywords

Apoptosis
Cancer cells
Carcinogenesis
Chemosensitivity
DNA-damage
KLF6
Krüppel-like factor
Proteasomal degradation
Ubiquitin

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@article{306db1671e8449cc8ec1fabcbef898a7,

title = "KLF6 degradation after apoptotic DNA damage",

abstract = "Kr{\"u}ppel-like factor 6 (KLF6) is a cancer gene (www.sanger.ac.uk/genetics/CGP/Census/). Here, we demonstrate that KLF6 protein is rapidly degraded when apoptosis is induced via the intrinsic pathway by cisplatin, adriamycin, or UVB irradiation in multiple cell lines (HCT116, SW40, HepG2, PC3-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR-90). KLF6 degradation occurred in the presence or absence of p53, was associated with ubiquitination, mediated by the proteasome (half-life 16 min, unstimulated), and independent of caspases and calpain. KLF6 was unchanged by apoptosis via the extrinsic/death-receptor pathway. Deregulation of KLF6 stability may alter its tumor suppressor function and/or the response of tumors to chemotherapeutics.",

keywords = "Apoptosis, Cancer cells, Carcinogenesis, Chemosensitivity, DNA-damage, KLF6, Kr{\"u}ppel-like factor, Proteasomal degradation, Ubiquitin",

author = "Banck, {Michaela S.} and Beaven, {Simon W.} and Goutham Narla and Walsh, {Martin J.} and Friedman, {Scott L.} and Beutler, {Andreas S.}",

note = "Funding Information: This work was supported by grants from the NIH (RO1DK37340 and DK56621 to SLF, HL067099 to MJW, and KO8DK068026-01A1 to MSB), the Department of Defense (PC041225 to MSB), Howard Hughes Medical Institute (Medical Student Research Fellowship to SWB), The Revson Foundation, and the American Society for Clinical Oncology (ASCO) (to MSB).",

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doi = "10.1016/j.febslet.2006.10.077",

language = "English",

volume = "580",

pages = "6981--6986",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Wiley-Blackwell",

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T1 - KLF6 degradation after apoptotic DNA damage

AU - Banck, Michaela S.

AU - Beaven, Simon W.

AU - Narla, Goutham

AU - Walsh, Martin J.

AU - Friedman, Scott L.

AU - Beutler, Andreas S.

N1 - Funding Information: This work was supported by grants from the NIH (RO1DK37340 and DK56621 to SLF, HL067099 to MJW, and KO8DK068026-01A1 to MSB), the Department of Defense (PC041225 to MSB), Howard Hughes Medical Institute (Medical Student Research Fellowship to SWB), The Revson Foundation, and the American Society for Clinical Oncology (ASCO) (to MSB).

PY - 2006/12/22

Y1 - 2006/12/22

N2 - Krüppel-like factor 6 (KLF6) is a cancer gene (www.sanger.ac.uk/genetics/CGP/Census/). Here, we demonstrate that KLF6 protein is rapidly degraded when apoptosis is induced via the intrinsic pathway by cisplatin, adriamycin, or UVB irradiation in multiple cell lines (HCT116, SW40, HepG2, PC3-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR-90). KLF6 degradation occurred in the presence or absence of p53, was associated with ubiquitination, mediated by the proteasome (half-life 16 min, unstimulated), and independent of caspases and calpain. KLF6 was unchanged by apoptosis via the extrinsic/death-receptor pathway. Deregulation of KLF6 stability may alter its tumor suppressor function and/or the response of tumors to chemotherapeutics.

AB - Krüppel-like factor 6 (KLF6) is a cancer gene (www.sanger.ac.uk/genetics/CGP/Census/). Here, we demonstrate that KLF6 protein is rapidly degraded when apoptosis is induced via the intrinsic pathway by cisplatin, adriamycin, or UVB irradiation in multiple cell lines (HCT116, SW40, HepG2, PC3-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR-90). KLF6 degradation occurred in the presence or absence of p53, was associated with ubiquitination, mediated by the proteasome (half-life 16 min, unstimulated), and independent of caspases and calpain. KLF6 was unchanged by apoptosis via the extrinsic/death-receptor pathway. Deregulation of KLF6 stability may alter its tumor suppressor function and/or the response of tumors to chemotherapeutics.

KW - Apoptosis

KW - Cancer cells

KW - Carcinogenesis

KW - Chemosensitivity

KW - DNA-damage

KW - KLF6

KW - Krüppel-like factor

KW - Proteasomal degradation

KW - Ubiquitin

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DO - 10.1016/j.febslet.2006.10.077

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SN - 0014-5793

VL - 580

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EP - 6986

JO - FEBS Letters

JF - FEBS Letters

IS - 30

ER -

KLF6 degradation after apoptotic DNA damage

Abstract

Keywords

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