PMID- 15131121
OWN - NLM
STAT- MEDLINE
DCOM- 20040817
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 29
DP  - 2004 Jul 16
TI  - Casein kinase 1alpha interacts with retinoid X receptor and interferes with 
      agonist-induced apoptosis.
PG  - 30844-9
AB  - Agonists of retinoid X receptors (RXRs), which include the natural 9-cis-retinoic 
      acid and synthetic analogs, are potent inducers of growth arrest and apoptosis in 
      some cancer cells. As such, they are being used in clinical trials for the 
      treatment and prevention of solid tumors and are used to treat cutaneous T cell 
      lymphoma. However, the molecular mechanisms that underlie the anti-cancer effects 
      of RXR agonists remain unclear. Here, we show that a novel pro-apoptotic pathway 
      that is induced by RXR agonist is negatively regulated by casein kinase 1alpha 
      (CK1alpha). CK1alpha associates with RXR in an agonist-dependent manner and 
      phosphorylates RXR. The ability of an RXR agonist to recruit CK1alpha to a 
      complex with RXR in cells correlates inversely with its ability to inhibit 
      growth. Remarkably, depletion of CK1alpha in resistant cells renders them 
      susceptible to RXR agonist-induced growth inhibition and apoptosis. Our study 
      shows that CK1alpha can promote cell survival by interfering with RXR 
      agonist-induced apoptosis. Inhibition of CK1alpha may enhance the anti-cancer 
      effects of RXR agonists.
FAU - Zhao, Yi
AU  - Zhao Y
AD  - Retinoid Research, Department of Biology, Allergan Inc., Irvine, California 
      92612, USA. zhao_yi@allergan.com
FAU - Qin, Suofu
AU  - Qin S
FAU - Atangan, Larissa I
AU  - Atangan LI
FAU - Molina, Yanira
AU  - Molina Y
FAU - Okawa, Yumiko
AU  - Okawa Y
FAU - Arpawong, Hieu T
AU  - Arpawong HT
FAU - Ghosn, Corine
AU  - Ghosn C
FAU - Xiao, Jia-Hao
AU  - Xiao JH
FAU - Vuligonda, Vidyasagar
AU  - Vuligonda V
FAU - Brown, Geoffrey
AU  - Brown G
FAU - Chandraratna, Roshantha A S
AU  - Chandraratna RA
LA  - eng
PT  - Journal Article
DEP - 20040506
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Ligands)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Casein Kinases)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Casein Kinases
MH  - Cell Line
MH  - Cell Survival
MH  - Dimerization
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - Genetic Vectors
MH  - HeLa Cells
MH  - Humans
MH  - Immunoblotting
MH  - Jurkat Cells
MH  - Ligands
MH  - Lymphoma, T-Cell/metabolism
MH  - Phosphorylation
MH  - Precipitin Tests
MH  - Protein Binding
MH  - Protein Kinases/chemistry/*metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Rats
MH  - Receptors, Retinoic Acid/chemistry/*metabolism
MH  - Retinoid X Receptors
MH  - Transcription Factors/chemistry/*metabolism
MH  - Transcriptional Activation
MH  - Transfection
EDAT- 2004/05/08 05:00
MHDA- 2004/08/18 05:00
CRDT- 2004/05/08 05:00
PHST- 2004/05/08 05:00 [pubmed]
PHST- 2004/08/18 05:00 [medline]
PHST- 2004/05/08 05:00 [entrez]
AID - S0021-9258(19)71108-9 [pii]
AID - 10.1074/jbc.M404651200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Jul 16;279(29):30844-9. doi: 10.1074/jbc.M404651200. Epub 2004 
      May 6.