PMID- 10490590
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 10
DP  - 1999 Oct
TI  - Mouse receptor interacting protein 3 does not contain a caspase-recruiting or a
      death domain but induces apoptosis and activates NF-kappaB.
PG  - 6500-8
AB  - The death domain-containing receptor superfamily and their respective downstream 
      mediators control whether or not cells initiate apoptosis or activate NF-kappaB, 
      events critical for proper immune system function. A screen for upstream
      activators of NF-kappaB identified a novel serine-threonine kinase capable of
      activating NF-kappaB and inducing apoptosis. Based upon domain organization and
      sequence similarity, this novel kinase, named mRIP3 (mouse receptor interacting
      protein 3), appears to be a new RIP family member. RIP, RIP2, and mRIP3 contain
      an N-terminal kinase domain that share 30 to 40% homology. In contrast to the
      C-terminal death domain found in RIP or the C-terminal caspase-recruiting domain 
      found in RIP2, the C-terminal tail of mRIP3 contains neither motif and is unique.
      Despite this feature, overexpression of the mRIP3 C terminus is sufficient to
      induce apoptosis, suggesting that mRIP3 uses a novel mechanism to induce death.
      mRIP3 also induced NF-kappaB activity which was inhibited by overexpression of
      either dominant-negative NIK or dominant-negative TRAF2. In vitro kinase assays
      demonstrate that mRIP3 is catalytically active and has autophosphorylation
      site(s) in the C-terminal domain, but the mRIP3 catalytic activity is not
      required for mRIP3 induced apoptosis and NF-kappaB activation. Unlike RIP and
      RIP2, mRIP3 mRNA is expressed in a subset of adult tissues and is thus likely to 
      be a tissue-specific regulator of apoptosis and NF-kappaB activity. While the
      lack of a dominant-negative mutant precludes linking mRIP3 to a known upstream
      regulator, characterizing the expression pattern and the in vitro functions of
      mRIP3 provides insight into the mechanism(s) by which cells modulate the balance 
      between survival and death in a cell-type-specific manner.
FAU - Pazdernik, N J
AU  - Pazdernik NJ
AD  - Departments of Biochemistry and Molecular Biology, Indiana University School of
      Medicine, Indianapolis, Indiana 46202, USA.
FAU - Donner, D B
AU  - Donner DB
FAU - Goebl, M G
AU  - Goebl MG
FAU - Harrington, M A
AU  - Harrington MA
LA  - eng
GR  - R01 AI042798/AI/NIAID NIH HHS/United States
GR  - R01 CA067891/CA/NCI NIH HHS/United States
GR  - AI42798/AI/NIAID NIH HHS/United States
GR  - CA73023/CA/NCI NIH HHS/United States
GR  - CA67891/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Fadd protein, mouse)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (NF-kappa B)
RN  - 0 (Proteins)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ripk1 protein, mouse)
RN  - EC 2.7.11.1 (Ripk3 protein, mouse)
RN  - EC 2.7.11.25 (NF-kappa B kinase)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - *Apoptosis
MH  - Base Sequence
MH  - Carrier Proteins/metabolism
MH  - Caspases/metabolism
MH  - DNA Damage
MH  - Fas-Associated Death Domain Protein
MH  - Gene Library
MH  - Genes, Reporter
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - NF-kappa B/*metabolism
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Kinases/*genetics
MH  - Protein-Serine-Threonine Kinases/*genetics
MH  - Proteins/genetics
MH  - Receptor-Interacting Protein Serine-Threonine Kinases
MH  - Sequence Homology, Amino Acid
MH  - TNF Receptor-Associated Factor 2
PMC - PMC84620
EDAT- 1999/09/22 00:00
MHDA- 1999/09/22 00:01
CRDT- 1999/09/22 00:00
PHST- 1999/09/22 00:00 [pubmed]
PHST- 1999/09/22 00:01 [medline]
PHST- 1999/09/22 00:00 [entrez]
AID - 10.1128/mcb.19.10.6500 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Oct;19(10):6500-8. doi: 10.1128/mcb.19.10.6500.