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MSSP promotes ras/myc cooperative cell transforming activity by binding to c‐Myc
Author(s) -
Niki Takeshi,
Izumi Sachiyo,
Saëgusa Yumiko,
Taira Takahiro,
Takai Toshiki,
IguchiAriga Sanae M. M.,
Ariga Hiroyoshi
Publication year - 2000
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.2000.00311.x
Subject(s) - biology , enhancer , transcription (linguistics) , dna , gene , cell , microbiology and biotechnology , rna , transcription factor , genetics , philosophy , linguistics
Background MSSPs, m yc s ingle s trand binding p roteins, were originally identified as proteins recognizing a putative replication origin/transcriptional enhancer in the human c‐Myc gene. The cDNAs encoding four of the family proteins, MSSP‐1, MSSP‐2, Scr2 and Scr3, were cloned. These proteins carry two copies of the putative RNA binding domains, RNP‐A and RNP‐B, and have been suggested to participate in DNA replication and cell cycle progression from the G 1 to the S phase. Results We report that MSSP‐1 and MSSP‐2 bound directly to the C‐terminal portion of c‐Myc, along with Max, side by side. MSSP, c‐Myc and Max formed a ternary complex in vivo , although MSSP did not directly associate with Max. The MSSP/Myc/Max ternary complex lost the binding activity to the E‐box sequence—the recognition sequence of c‐Myc/Max complex—thereby abrogating the E‐box‐dependent transcription activity of c‐Myc. MSSP specifically stimulated the cooperative transforming activity of c‐ myc with ras , in a manner dependent upon the RNP sequences, while mssp itself showed no transforming activity in mouse NIH3T3 cells. The NIH3T3 transformants, together with ras , myc and mssp , grew to form very large colonies in soft agar, as compared to those with ras plus myc or ras alone. Conclusions MSSP is a modulator of c‐Myc and the c‐Myc/MSSP complex may deregulate cell cycle controls and lead cells towards transforming pathways.