Cell. 1993 Nov 19;75(4):779-90.

A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.

Source

Department of Biology, University of California, San Diego, La Jolla 92093-0116.

Abstract

The ubiquitously expressed c-Abl tyrosine kinase is localized to the nucleus and binds to DNA. The DNA binding activity is regulated by cdc2-mediated phosphorylation, suggesting a cell cycle function for c-Abl. Here we show that the tyrosine kinase activity of nuclear c-Abl is regulated in the cell cycle through a specific interaction with the retinoblastoma protein (RB). A domain in the C-terminus of RB, outside of the A/B pocket, binds to the ATP-binding lobe of the c-Abl tyrosine kinase, resulting in kinase inhibition. The RB-c-Abl interaction is not affected by the viral oncoproteins that bind to RB. Hyperphosphorylation of RB correlates with release of c-Abl and activation of the tyrosine kinase in S phase cells. The nuclear c-Abl tyrosine kinase can enhance transcription, and this activity is inhibited by RB. Nuclear c-Abl is an S phase-activated tyrosine kinase that may participate directly in the regulation of transcription.

PMID:: 8242749; [PubMed - indexed for MEDLINE]

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

LinkOut - more resources

Full Text Sources

Other Literature Sources

COS Scholar Universe

Medical

RB1 Gene - Genetics Home Reference

Supplemental Content

Related citations

Abrogation of retinoblastoma protein function by c-Abl through tyrosine kinase-dependent and -independent mechanisms. [Mol Cell Biol. 1995]
Abrogation of retinoblastoma protein function by c-Abl through tyrosine kinase-dependent and -independent mechanisms.
Welch PJ, Wang JY. Mol Cell Biol. 1995 Oct; 15(10):5542-51.
Disruption of retinoblastoma protein function by coexpression of its C pocket fragment. [Genes Dev. 1995]
Disruption of retinoblastoma protein function by coexpression of its C pocket fragment.
Welch PJ, Wang JY. Genes Dev. 1995 Jan 1; 9(1):31-46.
Dual mechanisms for the inhibition of E2F binding to RB by cyclin-dependent kinase-mediated RB phosphorylation. [Mol Cell Biol. 1997]
Dual mechanisms for the inhibition of E2F binding to RB by cyclin-dependent kinase-mediated RB phosphorylation.
Knudsen ES, Wang JY. Mol Cell Biol. 1997 Oct; 17(10):5771-83.
Review Regulation of cell death by the Abl tyrosine kinase. [Oncogene. 2000]
Review Regulation of cell death by the Abl tyrosine kinase.
Wang JY. Oncogene. 2000 Nov 20; 19(49):5643-50.
Review Nuclear tyrosine kinases: from Abl to WEE1. [Curr Opin Cell Biol. 1996]
Review Nuclear tyrosine kinases: from Abl to WEE1.
Pendergast AM. Curr Opin Cell Biol. 1996 Apr; 8(2):174-81.

See reviews... See all...

Cited by 81 PubMed Central articles

Taccalonolides: a microtubule stabilizer poses a new puzzle with old pieces. [Cell Cycle. 2011]
Taccalonolides: a microtubule stabilizer poses a new puzzle with old pieces.
Sackett DL, Fojo T. Cell Cycle. 2011 Oct 1; 10(19):3233-4. Epub 2011 Oct 1.
Cell cycle-dependent phosphorylation of pRb-like protein in root meristem cells of Vicia faba. [Protoplasma. 2012]
Cell cycle-dependent phosphorylation of pRb-like protein in root meristem cells of Vicia faba.
Polit JT, Kaźmierczak A, Walczak-Drzewiecka A. Protoplasma. 2012 Jan; 249(1):131-7. Epub 2011 Mar 29.
Interaction of the retinoblastoma protein with Orc1 and its recruitment to human origins of DNA replication. [PLoS One. 2010]
Interaction of the retinoblastoma protein with Orc1 and its recruitment to human origins of DNA replication.
Mendoza-Maldonado R, Paolinelli R, Galbiati L, Giadrossi S, Giacca M. PLoS One. 2010 Nov 9; 5(11):e13720. Epub 2010 Nov 9.

See all...

Related information

Related Citations
Calculated set of PubMed citations closely related to the selected article(s) retrieved using a word weight algorithm. Related articles are displayed in ranked order from most to least relevant, with the “linked from” citation displayed first.
BioSystems
Pathways and biological systems (BioSystems) that cite the current articles. Citations are from the BioSystems source databases (KEGG and BioCyc).
Compound (MeSH Keyword)
PubChem chemical compound records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Gene
Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
Gene (GeneRIF)
Gene records that have the current articles as Reference into Function citations (GeneRIFs). NLM staff reviewing the literature while indexing MEDLINE add GeneRIFs manually.
Gene (OMIM)
Gene records associated with Online Mendelian Inheritance in Man (OMIM) records that cite the current articles in their reference lists.
HomoloGene
HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
Nucleotide (RefSeq)
NCBI nucleotide Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Nucleotide (Weighted)
Nucleotide records associated with the current articles through the Gene database. These are the related sequences on the Gene record that are added manually by NCBI.
OMIM (calculated)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as references in the light bulb links within or in the citations at the end of the OMIM record. The references available through the light bulb link are collected using the PubMed related articles algorithm to identify records with similar terminology to the OMIM record.
OMIM (cited)
Online Mendelian Inheritance in Man (OMIM) records that include the current articles as reference cited at the end of the OMIM record.
Protein (RefSeq)
NCBI protein Reference Sequences (RefSeqs) that are cited in the current articles, included in the corresponding Gene Reference into Function, or that include the PubMed articles as references.
Protein (Weighted)
Protein records associated with the current articles through related Gene database records. These are the related sequences on the Gene record that are added manually by NCBI.
Substance (MeSH Keyword)
PubChem chemical substance (submitted) records that are classified under the same Medical Subject Headings (MeSH) controlled vocabulary as the current articles.
Taxonomy via GenBank
Taxonomy records associated with the current articles through taxonomic information on related molecular database records (Nucleotide, Protein, Gene, SNP, Structure).
UniGene
UniGene clusters of expressed sequences that are associated with the current articles through references on the clustered sequence records and related Gene records.
GEO Profiles
Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
Cited in PMC
Full-text articles in the PubMed Central Database that cite the current articles.
Cited in Books
NCBI Bookshelf books that cite the current articles.

Recent activity

Clear Turn Off Turn On

A C-terminal protein-binding domain in the retinoblastoma protein regulates nucl...
A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
Cell. 1993 Nov 19 ;75(4):779-90.

PubMed
Dual mechanisms for the inhibition of E2F binding to RB by cyclin-dependent kina...
Dual mechanisms for the inhibition of E2F binding to RB by cyclin-dependent kinase-mediated RB phosphorylation.
Mol Cell Biol. 1997 Oct ;17(10):5771-83.

PubMed
The regions of the retinoblastoma protein needed for binding to adenovirus E1A o...
The regions of the retinoblastoma protein needed for binding to adenovirus E1A or SV40 large T antigen are common sites for mutations.
EMBO J. 1990 Apr ;9(4):1147-55.

PubMed
Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by si...
Cyclin D1/Cdk4 regulates retinoblastoma protein-mediated cell cycle arrest by site-specific phosphorylation.
Mol Biol Cell. 1997 Feb ;8(2):287-301.

PubMed
E2F: a link between the Rb tumor suppressor protein and viral oncoproteins.
E2F: a link between the Rb tumor suppressor protein and viral oncoproteins.
Science. 1992 Oct 16 ;258(5081):424-9.

PubMed

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

PubMed

Display Settings:

Send to: