Alternative titles; symbols
HGNC Approved Gene Symbol: RBBP4
Cytogenetic location: 1p35.1 Genomic coordinates (GRCh38): 1:32,651,208-32,686,211 (from NCBI)
The growth suppression function of the retinoblastoma protein (RB1; 614041) is thought to be mediated by RB1 binding to cellular proteins. Qian et al. (1993) showed that RBBP4, which they called RbAp48, is a major protein from HeLa cell lysates that specifically binds to the C terminus of RB1. By screening a HeLa cell cDNA library with a PCR product that was generated using oligonucleotides designed from RBBP4 peptide sequences, they isolated cDNAs encoding RBBP4. The predicted 425-amino acid RBBP4 protein has 30% sequence identity with the S. cerevisiae Msi1 protein, which is presumably a negative regulator of the Ras signal transduction pathway. RBBP4 from HeLa cell lysates has a molecular mass of 48 kD by Western blot analysis. Subcellular fractionation and immunocytochemistry studies showed that RBBP4 is a nuclear protein.
Qian and Lee (1995) found that the human and mouse RBBP4 proteins are identical. RBBP4 and RBBP7 (300825) have 89% amino acid identity and contain the same internal trp-asp (WD) repeats. RNase protection analysis detected Rbbp4 expression in all mouse tissues tested, although the levels varied dramatically between different tissues.
Qian et al. (1993) demonstrated that RBBP4 and RB1 formed complexes in vitro and in vivo; these complexes apparently involve direct interactions between the proteins. Qian et al. (1993) also demonstrated that RBBP4 could mimic the function of Msi1 in yeast.
By gel filtration of MOLT-4 human T cells, Schmit et al. (2007) identified RBAP48 as a subunit of the over 669-kD LIN complex. Other stable LIN complex components included LIN9 (609375), LIN37, LIN54 (613367), and BMYB (MYBL2; 601415). All endogenous or epitope-tagged LIN complex subunits coimmunoprecipitated with one another, and all were efficiently codepleted together with antibodies directed to LIN9. The LIN complex associated with E2F (see 189971)-regulated promoters in the T98G human glioblastoma cell line and was required for activation of G2/M genes. Depletion of LIN complex subunits had no significant effect on expression of G1/S genes.
Cryoelectron Microscopy
Kasinath et al. (2018) reported the cryoelectron microscopy structures of the human Polycomb repressive complex-2 (PRC2; see 605984) in a basal state and 2 distinct active states while in complex with its cofactors JARID2 (601594) and AEBP2 (617934). Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail. SUZ12 (606245) interacts with all other subunits within the assembly and thus contributes to the stability of the complex.
Kasinath, V., Faini, M., Poepsel, S., Reif, D., Feng, X. A., Stjepanovic, G., Aebersold, R., Nogales, E. Structures of human PRC2 with its cofactors AEBP2 and JARID2. Science 359: 940-944, 2018. [PubMed: 29348366] [Full Text: https://doi.org/10.1126/science.aar5700]
Qian, Y.-W., Lee, E. Y.-H. P. Dual retinoblastoma-binding proteins with properties related to a negative regulator of Ras in yeast. J. Biol. Chem. 270: 25507-25513, 1995. [PubMed: 7503932] [Full Text: https://doi.org/10.1074/jbc.270.43.25507]
Qian, Y.-W., Wang, Y.-C. J., Hollingsworth, R. E., Jr., Jones, D., Ling, N., Lee, E. Y.-H. P. A retinoblastoma-binding protein related to a negative regulator of Ras in yeast. Nature 364: 648-652, 1993. [PubMed: 8350924] [Full Text: https://doi.org/10.1038/364648a0]
Schmit, F., Korenjak, M., Mannefeld, M., Schmitt, K., Franke, C., von Eyss, B., Gagrica, S., Hanel, F., Brehm,A., Gaubatz, S. LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes. Cell Cycle 6: 1903-19113, 2007. [PubMed: 17671431] [Full Text: https://doi.org/10.4161/cc.6.15.4512]