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J. Biol. Chem., Vol. 276, Issue 4, 2766-2774, January 26, 2001
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) with Proliferating Cell Nuclear
Antigen Impedes Negative Growth Control*
, and
From the Fels Institute for Cancer Research and Molecular Biology
and the Department of Biochemistry, Temple University School of
Medicine, Philadelphia, Pennsylvania 19140
GADD45, MyD118, and
CR6 (also termed GADD45
, 
, and 
)
comprise a family of genes that encode for related proteins playing important roles in negative growth control, including growth
suppression. Data accumulated suggest that MyD118/GADD45/CR6 serve
similar but not identical functions along different apoptotic and
growth suppressive pathways. It is also apparent that individual
members of the MyD118/GADD45/CR6 family are differentially
induced by a variety of genetic and environmental stress agents. The
MyD118, CR6, and GADD45 proteins were shown to predominantly localize within the cell nucleus. Recently, we have shown that both MyD118 and
GADD45 interact with proliferating cell nuclear antigen (PCNA), a protein that plays a central role in DNA replication, DNA repair, and
cell cycle progression, as well as with the universal
cyclin-dependent kinase inhibitor p21. In this work we show
that also CR6 interacts with PCNA and p21. Moreover, it is shown that
CR6 interacts with PCNA via a domain that also mediates interaction of
both GADD45 and MyD118 with PCNA. Importantly, evidence has been
obtained that interaction of CR6 with PCNA impedes the function of this protein in negative growth control, similar to observations reported for MyD118 and GADD45 (1).
To whom correspondence may be addressed: Fels Inst. for Cancer
Research and Molecular Biology and Department of Biochemistry, Temple University School of Medicine, 3307 N. Broad St.,
Philadelphia, PA 19140. Tel.: 215-707-6903/2; Fax: 215-707-2805;
E-mail: lieberma@unix.temple.edu.
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