retinoblastoma-binding protein related to a negative regulator of Ras in yeast

• Published in: Nature (London) 1993-08, Vol.364 (6438), p.648-652
• Main Authors: Qian, Y.W, Wang, Y.C.J, Hollingsworth, R.E. Jr, Jones, D, Ling, N, Lee, E.Y.H.P
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; amino acid sequences; Base Sequence; binding proteins; Biological and medical sciences; Biotechnology; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; cDNA; Cell cycle, cell proliferation; Cell physiology; Cellular biology; Chromatin Assembly Factor-1; cloning; complex; DNA; DNA-Binding Proteins; Fundamental and applied biological sciences. Psychology; Fungal Proteins - chemistry; genes; Hot Temperature; Humanities and Social Sciences; Humans; letter; man; Molecular and cellular biology; Molecular Sequence Data; multidisciplinary; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; nucleotide sequence; nucleotide sequences; predictions; Protein Binding; protein p48; Proteins; RbAp48 gene; Recombinant Proteins - metabolism; Retinoblastoma Protein - metabolism; retinoblastoma-binding protein; Retinoblastoma-Binding Protein 4; Saccharomyces cerevisiae; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae Proteins; Science; Science (multidisciplinary); Sequence Homology, Amino Acid; Tumor Cells, Cultured; tumor suppressor genes; Yeast; Yeasts
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/364648a0

The growth suppression function of the retinoblastoma protein (Rb) is thought to be mediated by Rb binding to cellular proteins p48 is one of the major proteins that binds to a putative functional domain at the carboxy terminus of the Rb protein. Here we report the isolation of a full-length complementary DNA (RbAp4g) encoding p48. Complex formation between p48 and Rb occurs in vitro and in vivo, and apparently involves direct interaction between the proteins. Like Rb, p48 is a ubiquitously expressed nuclear protein. RbAp4g share sequence homology with MSI1, a negative regulator of the Ras-cyclic AMP pathway in the yeast Saccharomyces cerevisiae. Furthermore, like MSI1, human RbAp48 suppresses the heat-shock sensitivity of the yeast ira1 strains and RAS2(Val19) strains. Interaction with p48 may be one of the mechanisms for suppression of growth mediated by Rb.