MSSP promotes ras/myc cooperative cell transforming activity by binding to c-Myc.
BACKGROUND
MSSPs, myc single strand binding proteins, 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 G1 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.
Niki
T
T
Graduate School of Pharmaceutical Sciences and; College of Medical Technology, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
Izumi
S
S
Saëgusa
Y
Y
Taira
T
T
Takai
T
T
Iguchi-Ariga
S M
SM
Ariga
H
H
D016475:3T3 Cells / Q000473:pathology; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D011905:Genes, ras; D006367:HeLa Cells / Q000473:pathology; D006801:Humans; D051379:Mice; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499330:MAX protein, human; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; C086384:RBMS1 protein, human; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; C068422:Max protein, mouse