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Sumoylation of poly(ADP-ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function


Messner, S; Schuermann, D; Altmeyer, M; Kassner, I; Schmidt, D; Schär, P; Müller, S; Hottiger, M O (2009). Sumoylation of poly(ADP-ribose) polymerase 1 inhibits its acetylation and restrains transcriptional coactivator function. FASEB Journal, 23(11):3978-3989.

Abstract

Poly(ADP-ribose) polymerase 1 (PARP1)
is a chromatin-associated nuclear protein and functions
as a molecular stress sensor. At the cellular level,
PARP1 has been implicated in a wide range of processes,
such as maintenance of genome stability, cell
death, and transcription. PARP1 functions as a transcriptional
coactivator of nuclear factor B (NF-B)
and hypoxia inducible factor 1 (HIF1). In proteomic
studies, PARP1 was found to be modified by small
ubiquitin-like modifiers (SUMOs). Here, we characterize
PARP1 as a substrate for modification by SUMO1
and SUMO3, both in vitro and in vivo. PARP1 is
sumoylated at the single lysine residue K486 within its
automodification domain. Interestingly, modification
of PARP1 with SUMO does not affect its ADP-ribosylation
activity but completely abrogates p300-mediated
acetylation of PARP1, revealing an intriguing crosstalk
of sumoylation and acetylation on PARP1. Genetic
complementation of PARP1-depleted cells with wildtype
and sumoylation-deficient PARP1 revealed that
SUMO modification of PARP1 restrains its transcriptional
coactivator function and subsequently reduces
gene expression of distinct PARP1-regulated target
genes. Messner, S., Schuermann, D., Altmeyer, M.,
Kassner, I., Schmidt, D., Scha¨r, P., Mu¨ller, S., and
Hottiger, M. O. Sumoylation of poly(ADP-ribose) polymerase
1 inhibits its acetylation and restrains transcriptional
coactivator function.

Abstract

Poly(ADP-ribose) polymerase 1 (PARP1)
is a chromatin-associated nuclear protein and functions
as a molecular stress sensor. At the cellular level,
PARP1 has been implicated in a wide range of processes,
such as maintenance of genome stability, cell
death, and transcription. PARP1 functions as a transcriptional
coactivator of nuclear factor B (NF-B)
and hypoxia inducible factor 1 (HIF1). In proteomic
studies, PARP1 was found to be modified by small
ubiquitin-like modifiers (SUMOs). Here, we characterize
PARP1 as a substrate for modification by SUMO1
and SUMO3, both in vitro and in vivo. PARP1 is
sumoylated at the single lysine residue K486 within its
automodification domain. Interestingly, modification
of PARP1 with SUMO does not affect its ADP-ribosylation
activity but completely abrogates p300-mediated
acetylation of PARP1, revealing an intriguing crosstalk
of sumoylation and acetylation on PARP1. Genetic
complementation of PARP1-depleted cells with wildtype
and sumoylation-deficient PARP1 revealed that
SUMO modification of PARP1 restrains its transcriptional
coactivator function and subsequently reduces
gene expression of distinct PARP1-regulated target
genes. Messner, S., Schuermann, D., Altmeyer, M.,
Kassner, I., Schmidt, D., Scha¨r, P., Mu¨ller, S., and
Hottiger, M. O. Sumoylation of poly(ADP-ribose) polymerase
1 inhibits its acetylation and restrains transcriptional
coactivator function.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease
Dewey Decimal Classification:570 Life sciences; biology
Date:2009
Deposited On:01 Mar 2010 15:04
Last Modified:10 Dec 2017 06:25
Publisher:Federation of American Societies for Experimental Biology
ISSN:0892-6638
Publisher DOI:https://doi.org/10.1096/fj.09-137695
PubMed ID:19622798

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