[The molecular mechanism of survivin expression in activated human peripheral lymphocytes].
OBJECTIVE
Investigate the molecular mechanism of regulating survivin expression and related signal transduction pathway, molecular cascade reaction and biological effects in activated PBMC.


METHODS
The expression of survivin and related proteins were detected by Western blot in PBMC stimulated by PHA and rhIL-2 with or without JAK inhibitor-AG490 treatment, and FCM was performed to analyze cell cycle and cell division.


RESULTS
Our results indicated that molecular and cellular reactions in PBMC activated by PHA and rhIL-2 were dependent on time series. At first, the phosphorylation of Stat3 and Stat5 were observed, then, protein levels of CyclinD3 and CyclinE increased, and the stimulated PBMC began to enter to S phage with survivin protein expression was initiated, which at last resulted in cell division with dramatically increasing expression of survivin protein. AG490 could significantly inhibit all these reactions but had no effect on the expressions of the cell cycle inhibitor-P21 and anti-apoptosis protein-Bcl-2.


CONCLUSIONS
The expression of survivin in stimulated PBMC was dependent on the primarily activated JAK-STAT pathway, which upregulated CyclinD3 and CyclinE protein levels, initiated the cell cycle progression, and induced cell cycle-dependent survivin expression, and so survivin was involved in cell division and cell proliferation.
Dong
Yan
Y
Institute of Radiation Medicine, Beijing 100850, China.
Mei
Zhu-zhong
ZZ
Qian
Jun-jie
JJ
Song
Yi
Y
Tian
Bao-lei
BL
Liu
Bin
B
Sun
Zhi-xian
ZX
D015815:Cell Adhesion Molecules; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D000077022:Survivin; D020032:Tyrphostins / Q000494:pharmacology
C107489:BIRC5 protein, human; D015815:Cell Adhesion Molecules; C470661:ICAM-L protein, Leishmania gerbelli; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D015800:Protozoan Proteins; D050796:STAT3 Transcription Factor; D000077022:Survivin; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide