PMID- 21283629
OWN - NLM
STAT- MEDLINE
DCOM- 20110802
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 1
DP  - 2011 Jan 24
TI  - LZAP inhibits p38 MAPK (p38) phosphorylation and activity by facilitating p38 
      association with the wild-type p53 induced phosphatase 1 (WIP1).
PG  - e16427
LID - 10.1371/journal.pone.0016427 [doi]
LID - e16427
AB  - LZAP (Cdk5rap3, C53) is a putative tumor suppressor that inhibits RelA, Chk1 and 
      Chk2 and activates p53. LZAP is lost in a portion of human head and neck squamous 
      cell carcinoma and experimental loss of LZAP expression is associated with 
      enhanced invasion, xenograft tumor growth and angiogenesis. p38 MAPK can increase 
      or decrease proliferation and cell death depending on cellular context. LZAP has 
      no known enzymatic activity, implying that its biological functions are likely 
      mediated by its protein-protein interactions. To gain further insight into LZAP 
      activities, we searched for LZAP-associated proteins (LAPs). Here we show that 
      the LZAP binds p38, alters p38 cellular localization, and inhibits basal and 
      cytokine-stimulated p38 activity. Expression of LZAP inhibits p38 phosphorylation 
      in a dose-dependent fashion while loss of LZAP enhances phosphorylation and 
      activation with resultant phosphorylation of p38 downstream targets. 
      Mechanistically, the ability of LZAP to alter p38 phosphorylation depended, at 
      least partially, on the p38 phosphatase, Wip1. Expression of LZAP increased both 
      LZAP and Wip1 binding to p38. Taken together, these data suggest that LZAP 
      activity includes inhibition of p38 phosphorylation and activation.
FAU - An, Hanbing
AU  - An H
AD  - Department of Otolaryngology, Vanderbilt University, Nashville, Tennessee, United 
      States of America.
FAU - Lu, Xinyuan
AU  - Lu X
FAU - Liu, Dan
AU  - Liu D
FAU - Yarbrough, Wendell G
AU  - Yarbrough WG
LA  - eng
GR  - R01 DE013173/DE/NIDCR NIH HHS/United States
GR  - R56 DE013173/DE/NIDCR NIH HHS/United States
GR  - 2R56 DE013173-10/DE/NIDCR NIH HHS/United States
GR  - # 2R01 DE013173/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110124
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CDK5RAP3 protein, human)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.16 (PPM1D protein, human)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 2C)
SB  - IM
MH  - Cell Compartmentation
MH  - Cell Cycle Proteins
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/metabolism/*physiology
MH  - Nerve Tissue Proteins/metabolism/*physiology
MH  - Phosphoprotein Phosphatases/*metabolism
MH  - Phosphorylation
MH  - Protein Binding/physiology
MH  - Protein Phosphatase 2C
MH  - Tumor Suppressor Protein p53/genetics/metabolism
MH  - Tumor Suppressor Proteins
MH  - p38 Mitogen-Activated Protein Kinases/analysis/antagonists & 
      inhibitors/*metabolism
PMC - PMC3026010
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/02/02 06:00
MHDA- 2011/08/04 06:00
PMCR- 2011/01/24
CRDT- 2011/02/02 06:00
PHST- 2010/09/27 00:00 [received]
PHST- 2010/12/16 00:00 [accepted]
PHST- 2011/02/02 06:00 [entrez]
PHST- 2011/02/02 06:00 [pubmed]
PHST- 2011/08/04 06:00 [medline]
PHST- 2011/01/24 00:00 [pmc-release]
AID - PONE-D-10-03186 [pii]
AID - 10.1371/journal.pone.0016427 [doi]
PST - epublish
SO  - PLoS One. 2011 Jan 24;6(1):e16427. doi: 10.1371/journal.pone.0016427.