PMID- 19586909
OWN - NLM
STAT- MEDLINE
DCOM- 20091102
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 284
IP  - 37
DP  - 2009 Sep 11
TI  - Endogenous human CaMKII inhibitory protein suppresses tumor growth by inducing 
      cell cycle arrest and apoptosis through down-regulation of the 
      phosphatidylinositide 3-kinase/Akt/HDM2 pathway.
PG  - 24773-82
LID - 10.1074/jbc.M109.028621 [doi]
AB  - Inhibition of calcium/calmodulin-dependent protein kinase II (CaMKII) results in 
      hypophosphorylation of CaMKII substrates and in some cases suppresses cell 
      growth. We previously presented the first report of the human CaMKII inhibitory 
      protein, hCaMKIINbeta. Here we report the functional characterization of 
      hCaMKIINbeta in ovarian cancer cells. We showed that hCaMKIINbeta was highly 
      expressed in normal ovarian tissues but was not detected in human ovarian 
      adenocarcinoma, indicating that decreased expression of hCaMKIINbeta may be 
      involved in the pathogenesis of human ovarian adenocarcinoma. As an endogenous 
      CaMKII inhibitor, hCaMKIINbeta could significantly inhibit the growth of human 
      ovarian cancer cells in vitro. In vivo, hCaMKIINbeta decreased the tumorigenicity 
      and growth of HO-8910PM human ovarian cancer cells and prolonged the survival of 
      tumor-bearing mice. hCaMKIINbeta blocked cell cycle progression and induced 
      apoptosis of HO-8910PM cells, which was correlated with the up-regulation of p21, 
      p53, and Bax and the down-regulation of cyclin A, cyclin D1, cyclin E, CDK2, 
      phosphorylated retinoblastoma, and Bcl-2. We further demonstrated that 
      hCaMKIINbeta-mediated CaMKII inhibition suppressed Akt activation, leading to the 
      down-regulation of HDM2, which was responsible for the up-regulation of p53 and 
      p21 in human ovarian cancer cells. The tumor-suppressive effect and the negative 
      expression in human ovarian cancer tissues suggest that hCaMKIINbeta may play an 
      important role in the regulation of tumor cell growth, possibly contributing to 
      the development of new therapeutic strategies for ovarian cancer.
FAU - Ma, Shenglin
AU  - Ma S
AD  - Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang, China.
FAU - Yang, Yunshan
AU  - Yang Y
FAU - Wang, Chunmei
AU  - Wang C
FAU - Hui, Ning
AU  - Hui N
FAU - Gu, Linhui
AU  - Gu L
FAU - Zhong, Haijun
AU  - Zhong H
FAU - Cai, Zhijian
AU  - Cai Z
FAU - Wang, Qingqing
AU  - Wang Q
FAU - Zhang, Qinghua
AU  - Zhang Q
FAU - Li, Nan
AU  - Li N
FAU - Cao, Xuetao
AU  - Cao X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20090708
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Mdm2 protein, mouse)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
SB  - IM
ECI - J Biol Chem. 2020 Jun 26;295(26):8882. PMID: 32591458
RIN - J Biol Chem. 2021 Jan-Jun;296:100752. PMID: 34237887
MH  - Animals
MH  - *Apoptosis
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/*metabolism
MH  - Cell Line, Tumor
MH  - Female
MH  - *Gene Expression Regulation, Enzymologic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Models, Biological
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Proto-Oncogene Proteins c-mdm2/*metabolism
PMC - PMC2757181
EDAT- 2009/07/10 09:00
MHDA- 2009/11/03 06:00
PMCR- 2010/09/11
CRDT- 2009/07/10 09:00
PHST- 2009/07/10 09:00 [entrez]
PHST- 2009/07/10 09:00 [pubmed]
PHST- 2009/11/03 06:00 [medline]
PHST- 2010/09/11 00:00 [pmc-release]
AID - S0021-9258(20)30566-4 [pii]
AID - M109.028621 [pii]
AID - 10.1074/jbc.M109.028621 [doi]
PST - ppublish
SO  - J Biol Chem. 2009 Sep 11;284(37):24773-82. doi: 10.1074/jbc.M109.028621. Epub 
      2009 Jul 8.