[Biological mechanism of full-length form of spleen tyrosine kinase regulating gene transcription in breast cancer cells].
OBJECTIVE
Full-length form of spleen tyrosine kinase [Syk(L)] is a tumor suppressor gene in breast cancer, which may translocate into cell nucleus and act as a transcriptional repressor. This study was to explore the mechanism of Syk(L) regulated gene transcription in breast cancer cells.


METHODS
Flag-tagged Syk(L) was transfected into human embryonic kidney (HEK) 293 cells, and the interaction of Syk(L) and histone deacetylases (HDACs) was detected by immunoprecipitation. The binding of endogenous HDAC1 and Syk(L) in breast cancer cell line MB468 was also detected by immunoprecipitation. Flag-tagged Syk(L) domains SH2, KD, and IDB(L) were transfected into HEK293 cells, respectively, and their interaction with HDAC1 was detected. The activity of HDACs in the immunoprecipited complexes of Syk(L) was tested by HDAC activity detecting system.


RESULTS
Exogenous Syk(L) was bound with HDAC1, 3, 6, and 7 in HEK293 cells, and endogenous Syk(L) was bound with HDAC1 in MB468 cells. SH2 and KD, but not IDB(L), were coimmunoprecipitated with HDAC1. The activity of HDACs was detected in the immunoprecipited complexes of Syk(L).


CONCLUSIONS
Syk(L) regulates gene transcription in breast cancer by binding with HDACs to form transcription repressive complexes.
Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, PR China.
Lei
L
Wang
Ying
Y
Hu
Zu-Li
ZL
Yang
Xin-Ming
XM
Song
Jian-Ping
JP
Wang
D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D004622:Embryo, Mammalian; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D010957:Plasmids; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D000072377:Syk Kinase; D014162:Transfection
D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D006655:Histone Deacetylases