PMID- 22748127
OWN - NLM
STAT- MEDLINE
DCOM- 20121108
LR  - 20211021
IS  - 1742-4658 (Electronic)
IS  - 1742-464X (Print)
IS  - 1742-464X (Linking)
VI  - 279
IP  - 17
DP  - 2012 Sep
TI  - Lens epithelium-derived growth factor deSumoylation by Sumo-specific protease-1 
      regulates its transcriptional activation of small heat shock protein and the 
      cellular response.
PG  - 3048-70
LID - 10.1111/j.1742-4658.2012.08686.x [doi]
AB  - Lens epithelium-derived growth factor (LEDGF), a ubiquitously expressed nuclear 
      protein, acts by interacting with DNA and protein and is involved in widely 
      varying cellular functions. Despite its importance, the mechanism(s) that 
      regulate naturally occurring LEDGF activity are unidentified. In the present 
      study, we report that LEDGF is constitutively Sumoylated, and that the dynamical 
      regulatory mechanism(s) (i.e. Sumoylation and deSumoylation) act as a molecular 
      switch in modulating the DNA-binding and transcriptional activity of LEDGF with 
      the functional consequences. Using bioinformatics analysis coupled with in vitro 
      and in vivo Sumoylation assays, we found that lysine (K) 364 of LEDGF was 
      Sumoylated, repressing its transcriptional activity. Conversely, mutation of K364 
      to arginine (R) or deSumoylation by small ubiquitin-like modifier (Sumo)-specific 
      protease-1, a nuclear deSumoylase, enhanced the transactivation capacity of LEDGF 
      and its cellular abundance. The enhancements were directly correlated with an 
      increase in the DNA-binding activity and small heat shock protein transcription 
      of LEDGF, whereas the process was reversed in cells overexpressing Sumo1. 
      Interestingly, cells expressing Sumoylation-deficient pEGFP-K364R protein showed 
      increased cellular survival compared to wild-type LEDGF protein. The findings 
      provide insights into the regulation and regulatory functions of LEDGF in 
      Sumoylation-dependent transcriptional control that may be essential for modifying 
      the physiology of cells to maintain cellular homeostasis. These studies also 
      provide new evidence of the important role of post-translational modification in 
      controlling LEDGF function.
CI  - (c) 2012 The Authors Journal compilation (c) 2012 FEBS.
FAU - Ishihara, Keiichi
AU  - Ishihara K
AD  - Department of Ophthalmology and Visual Sciences, University of Nebraska Medical 
      Center, Omaha, NE, USA.
FAU - Fatma, Nigar
AU  - Fatma N
FAU - Bhargavan, Biju
AU  - Bhargavan B
FAU - Chhunchha, Bhavana
AU  - Chhunchha B
FAU - Kubo, Eri
AU  - Kubo E
FAU - Dey, Sanjib
AU  - Dey S
FAU - Takamura, Yoshihiro
AU  - Takamura Y
FAU - Kumar, Anil
AU  - Kumar A
FAU - Singh, Dhirendra P
AU  - Singh DP
LA  - eng
GR  - R01 EY013394/EY/NEI NIH HHS/United States
GR  - R01 EY017613/EY/NEI NIH HHS/United States
GR  - EY-13394/EY/NEI NIH HHS/United States
GR  - EY017613/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120716
PL  - England
TA  - FEBS J
JT  - The FEBS journal
JID - 101229646
RN  - 0 (DNA Primers)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (lens epithelium-derived growth factor)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.- (SENP1 protein, human)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Cysteine Endopeptidases
MH  - DNA Primers
MH  - Endopeptidases/*metabolism
MH  - Heat-Shock Proteins/*genetics
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Molecular Sequence Data
MH  - Sequence Homology, Amino Acid
MH  - Sumoylation
MH  - *Transcriptional Activation
PMC - PMC3470485
MID - NIHMS394060
EDAT- 2012/07/04 06:00
MHDA- 2012/11/09 06:00
PMCR- 2013/09/01
CRDT- 2012/07/04 06:00
PHST- 2012/07/04 06:00 [entrez]
PHST- 2012/07/04 06:00 [pubmed]
PHST- 2012/11/09 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - 10.1111/j.1742-4658.2012.08686.x [doi]
PST - ppublish
SO  - FEBS J. 2012 Sep;279(17):3048-70. doi: 10.1111/j.1742-4658.2012.08686.x. Epub 
      2012 Jul 16.