PMID- 24170542
OWN - NLM
STAT- MEDLINE
DCOM- 20140821
LR  - 20211021
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 386
IP  - 1-2
DP  - 2014 Jan
TI  - Adhesion to fibronectin induces p27(Kip1) nuclear accumulation through 
      down-regulation of Jab1 and contributes to cell adhesion-mediated drug resistance 
      (CAM-DR) in RPMI 8,226 cells.
PG  - 177-87
LID - 10.1007/s11010-013-1856-7 [doi]
AB  - Mounting evidence has been shown that integrin-mediated cellular adhesion confers 
      resistance to chemotherapy of multiple myeloma. The molecular mechanism 
      underlying cell adhesion-mediated drug resistance (CAM-DR) is, however, poorly 
      understood. In this report, we demonstrated that RPMI 8,226 cells accumulated 
      p27(Kip1) in the nucleus when they were adhered to fibronectin (FN). The 
      adhesion-mediated p27(Kip1) nuclear recruitment was regulated via the 
      down-regulation of Jab1, a negative regulator of cell cycle. Overexpression of 
      Jab1 reversed the elevated p27(Kip1) in the nucleus, which needed phosphorylation 
      of p27(Kip1) on Serine 10, whereas inhibition of Jab1 by siRNA further increased 
      the elevated p27(Kip1). Furthermore, we found overexpression of Jab1 did not 
      affect 8,226 cells adhesion to FN, but reversed doxorubicin or 
      mitoxantrone-induced CAM-DR phenotype. In conclusion, our data suggest that Jab1 
      plays an important role in CAM-DR, which depends on pSer10-p27(Kip1)-mediated 
      subcellular localization of p27(Kip1). The understanding of this novel molecular 
      mechanism may prove valuable in designing new therapeutic approaches for CAM-DR 
      in Multiple myeloma.
FAU - Fei, Min
AU  - Fei M
AD  - Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow 
      University, Suzhou, Jiangsu, China.
FAU - Hang, Qinglei
AU  - Hang Q
FAU - Hou, Sicong
AU  - Hou S
FAU - He, Songbin
AU  - He S
FAU - Ruan, Changgeng
AU  - Ruan C
LA  - eng
PT  - Journal Article
DEP - 20131030
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (CDKN1B protein, human)
RN  - 0 (Fibronectins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - EC 3.4.-.- (COPS5 protein, human)
RN  - EC 3.4.19.12 (COP9 Signalosome Complex)
SB  - IM
MH  - COP9 Signalosome Complex
MH  - *Cell Adhesion
MH  - Cell Line, Tumor
MH  - Cell Nucleus/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p27/*metabolism
MH  - *Down-Regulation
MH  - Drug Resistance, Neoplasm
MH  - Fibronectins/*metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*metabolism
MH  - Microscopy, Fluorescence
MH  - Multiple Myeloma/metabolism/*pathology
MH  - Peptide Hydrolases/*metabolism
MH  - Phosphorylation
EDAT- 2013/10/31 06:00
MHDA- 2014/08/22 06:00
CRDT- 2013/10/31 06:00
PHST- 2013/03/21 00:00 [received]
PHST- 2013/09/27 00:00 [accepted]
PHST- 2013/10/31 06:00 [entrez]
PHST- 2013/10/31 06:00 [pubmed]
PHST- 2014/08/22 06:00 [medline]
AID - 10.1007/s11010-013-1856-7 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2014 Jan;386(1-2):177-87. doi: 10.1007/s11010-013-1856-7. Epub 
      2013 Oct 30.