PMID- 22582703
OWN - NLM
STAT- MEDLINE
DCOM- 20120926
LR  - 20211021
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Print)
IS  - 0264-6021 (Linking)
VI  - 445
IP  - 3
DP  - 2012 Aug 1
TI  - The MEKK1 SWIM domain is a novel substrate receptor for c-Jun ubiquitylation.
PG  - 431-9
LID - 10.1042/BJ20120406 [doi]
AB  - MEKK1 [MAPK (mitogen-activated protein kinase)/ERK 
      (extracellular-signal-regulated kinase) kinase kinase 1] is a MAP3K (MAPK kinase 
      kinase) that regulates MAPK activation, and is the only known mammalian kinase 
      that is also a ubiquitin ligase. MEKK1 contains a RING domain within its 
      N-terminal regulatory region, and MEKK1 has been shown to ubiquitylate the AP-1 
      (activator protein 1) transcription factor protein c-Jun, but the mechanism by 
      which MEKK1 interacts with c-Jun to induce ubiquitylation has not been defined. 
      Proximal to the RING domain is a SWIM (SWI2/SNF2 and MuDR) domain of undetermined 
      function. In the present study, we demonstrate that the MEKK1 SWIM domain, but 
      not the RING domain, directly associates with the c-Jun DNA-binding domain, and 
      that the SWIM domain is required for MEKK1-dependent c-Jun ubiquitylation. We 
      further show that this MEKK1 SWIM-Jun interaction is specific, as SWIM domains 
      from other proteins failed to bind c-Jun. We reveal that, although the Jun and 
      Fos DNA-binding domains are highly conserved, the MEKK1 SWIM domain does not bind 
      Fos. Finally, we identify the sequence unique to Jun proteins required for 
      specific interaction with the MEKK1 SWIM domain. Therefore we propose that the 
      MEKK1 SWIM domain represents a novel substrate-binding domain necessary for 
      direct interaction between c-Jun and MEKK1 that promotes MEKK1-dependent c-Jun 
      ubiquitylation.
FAU - Rieger, Michael A
AU  - Rieger MA
AD  - Department of Molecular Pharmacology and Therapeutics, Stritch School of 
      Medicine, Loyola University Chicago, Maywod, IL 60153, USA.
FAU - Duellman, Tyler
AU  - Duellman T
FAU - Hooper, Christopher
AU  - Hooper C
FAU - Ameka, Magdalene
AU  - Ameka M
FAU - Bakowska, Joanna C
AU  - Bakowska JC
FAU - Cuevas, Bruce D
AU  - Cuevas BD
LA  - eng
GR  - K01 CA120881/CA/NCI NIH HHS/United States
GR  - CA120881/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Catalytic Domain
MH  - Cell Line
MH  - Cell Survival
MH  - Enzyme Activation
MH  - HEK293 Cells
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/chemistry/*metabolism
MH  - MAP Kinase Kinase Kinase 1/*chemistry/genetics/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mice, Knockout
MH  - Molecular Sequence Data
MH  - Protein Structure, Tertiary
MH  - Recombinant Fusion Proteins/chemistry/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Substrate Specificity
MH  - Ubiquitination
PMC - PMC3653270
MID - NIHMS464532
EDAT- 2012/05/16 06:00
MHDA- 2012/09/27 06:00
PMCR- 2013/08/01
CRDT- 2012/05/16 06:00
PHST- 2012/05/16 06:00 [entrez]
PHST- 2012/05/16 06:00 [pubmed]
PHST- 2012/09/27 06:00 [medline]
PHST- 2013/08/01 00:00 [pmc-release]
AID - BJ20120406 [pii]
AID - 10.1042/BJ20120406 [doi]
PST - ppublish
SO  - Biochem J. 2012 Aug 1;445(3):431-9. doi: 10.1042/BJ20120406.