ArticleMolecular and cellular biology1993
A bipartite nuclear localization signal in the retinoblastoma gene product and its importance for biological activity.
Article in Molecular and cellular biology, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 92 citations in OpenAlex.
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- Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis.Nature communications · 2020Article
- Immunohistochemical detection of p53, PTEN, Rb, and p16 in canine osteosarcoma using tissue microarray.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2018Article
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- APC/C and retinoblastoma interaction: cross-talk of retinoblastoma protein with the ubiquitin proteasome pathway.Bioscience reports · 2016Review
- Rb1/105 gene alterations and head and neck carcinogenesis.Molecular biology reports · 2012Article
- RB116: an RB1+ retinoblastoma cell line expressing primitive markers.Molecular vision · 2012Article
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- Mechanism of microtubule-facilitated "fast track" nuclear import.The Journal of biological chemistry · 2011Article
- Acetylation of Rb by PCAF is required for nuclear localization and keratinocyte differentiation.Journal of cell science · 2010Article
- Regulation of the Chlamydomonas cell cycle by a stable, chromatin-associated retinoblastoma tumor suppressor complex.The Plant cell · 2010Article
- Nuclear localization sequences in cytomegalovirus capsid assembly proteins (UL80 proteins) are required for virus production: inactivating NLS1, NLS2, or both affects replication to strikingly different extents.Journal of virology · 2008Article
- Article
- Parafibromin is a nuclear protein with a functional monopartite nuclear localization signal.Oncogene · 2007Article
- Specific amino acid residues in the basic helix-loop-helix domain of SRC-3 are essential for its nuclear localization and proteasome-dependent turnover.Molecular and cellular biology · 2007Article
- Conserved and specific functions of mammalian ssu72.Nucleic acids research · 2005Article
- Article
- Retinoblastoma tumor suppressor: analyses of dynamic behavior in living cells reveal multiple modes of regulation.Molecular and cellular biology · 2003Article
- Lamin A/C binding protein LAP2alpha is required for nuclear anchorage of retinoblastoma protein.Molecular biology of the cell · 2002Article
- Changes in retinoblastoma gene expression during cervical cancer progression.International journal of experimental pathology · 2002Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The retinoblastoma gene product, p110RB1, appears to regulate cell growth by modulating the activities of nuclear transcription factors. The elements that specify the transport of p110RB1 into the nucleus have not yet been explored. We now report the identification of a basic region, KRSAEGGNPPKPLKKLR, in the C terminus of p110RB1, which has sequence similarity to known bipartite nuclear localization signals (NLSs). A two-amino-acid mutation introduced into this putative NLS [to give mutant NLS(NQ)] or deletion of the entire NLS (delta NLS) abrogated exclusive nuclear localization, yielding proteins which were distributed either equally throughout the cell or predominantly in the cytoplasm. A mutant protein [NLS(NQ)/delta 22] containing both the mutated NLS and a deletion of exon 22, previously shown to disrupt the interaction of p110RB1 with several cellular transcription factors and oncoproteins, accumulated only in the cytoplasm. When fused to the C terminus of Escherichia coli beta-galactosidase, the RB1 NLS directed this protein to the nucleus, indicating that the motif is not only necessary but also sufficient for nuclear transport. Neither NLS(NQ) nor delta NLS was hyperphosphorylated in vivo, but both retained their abilities to interact, in vitro, with simian virus 40 large T antigen, adenovirus E1a, and the cellular transcription factor E2F. When transfected at multiple copy number, the NLS mutant alleles displayed reduced biological activity, measured by inhibition of growth of the osteogenic sarcoma cell line Saos-2, which has no wild-type RB1. Naturally occurring mutations and deletions in exon 25 of RB1 which disrupt the NLS may lead to partial or complete inactivation of p110RB1 and may be responsible for some retinoblastoma and other tumors.
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