Identification of a growth suppression domain within the retinoblastoma gene product.
To date, all naturally occurring retinoblastoma susceptibility gene (RB) mutations known to be compatible with stable protein expression map to the T/E1A and cellular protein-binding region (the "pocket" domain). This domain extends from residue 379 to 792. When full-length RB and certain truncated forms were synthesized in human RB -/- cells, we found that the minimal region necessary for overt growth suppression extended from residue 379 to 928. A functional pocket domain and sequences extending from the carboxy-terminal boundary of the pocket to the carboxyl terminus of the protein were both necessary for growth suppression. Both sets of sequences were also required for E2F binding; hence, the two functions may be linked.
Qin
X Q
XQ
Division of Neoplastic Disease Mechanisms, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Chittenden
T
T
Livingston
D M
DM
Kaelin
W G
WG
D017456:Adenovirus Early Proteins; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006131:Growth Inhibitors / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*
D017456:Adenovirus Early Proteins; D000952:Antigens, Polyomavirus Transforming; D006131:Growth Inhibitors; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein