Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1

J M Kearsey; P J Coates; A R Prescott; E Warbrick; P A Hall

Gadd45 is a nuclear cell cycle regulated protein which interacts with p21Cip1

Oncogene. 1995 Nov 2;11(9):1675-83.

Authors

J M Kearsey¹, P J Coates, A R Prescott, E Warbrick, P A Hall

Affiliation

¹ Department of Pathology, University of Dundee, Scotland.

PMID: 7478594

Abstract

GADD45 was originally identified as a cDNA clone induced by growth arrest and DNA damage. We show that Gadd45 is a nuclear protein, widely expressed in normal tissues, particularly in quiescent cellular populations. Using cell synchronisation methods we show that Gadd45 levels are highest in the G1 phase of the cell cycle, and are greatly reduced during S phase. Immunoprecipitation of Gadd45 from mammalian cells reveals that it is tightly associated with a protein which reacts with antibodies to the cyclin dependent kinase inhibitor p21Cip1. Binding of recombinant Gadd45 protein to overlapping p21Cip1 peptides in ELISA assays and use of the yeast two hybrid assay show that Gadd45 directly interacts with this cell cycle inhibitor. These data suggest that Gadd45 may act in the regulation of the cell cycle. It is postulated that the interactions of Gadd45 with both p21Cip1 and PCNA are important for the modulation of cell cycles, and for the inhibition of DNA replication.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Amino Acid Sequence
Animals
Antibodies
Blotting, Western
Cell Cycle* / radiation effects
Cloning, Molecular
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / biosynthesis
Cyclins / isolation & purification
Cyclins / metabolism*
Enzyme-Linked Immunosorbent Assay
G1 Phase
GADD45 Proteins
Gamma Rays
Homeostasis
Humans
Immunohistochemistry
Intracellular Signaling Peptides and Proteins
Mammals
Mice
Mice, Inbred Strains
Molecular Sequence Data
Nuclear Proteins / biosynthesis
Nuclear Proteins / metabolism
Peptide Fragments / chemistry
Peptide Fragments / immunology
Polymerase Chain Reaction
Protein Binding
Protein Biosynthesis
Protein Kinase Inhibitors*
Proteins / isolation & purification
Proteins / metabolism*
Recombinant Proteins / biosynthesis
Recombinant Proteins / isolation & purification
Recombinant Proteins / metabolism
S Phase

Substances

Antibodies
CDKN1A protein, human
Cdkn1a protein, mouse
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
Intracellular Signaling Peptides and Proteins
Nuclear Proteins
Peptide Fragments
Protein Kinase Inhibitors
Proteins
Recombinant Proteins