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J. Biol. Chem., Vol. 275, Issue 22, 16810-16819, June 2, 2000
From the Fels Institute for Cancer Research and Molecular
Biology and the Department of Biochemistry, Temple University
School of Medicine, Philadelphia, Pennsylvania 19140
MyD118 and Gadd45 are
related genes encoding for proteins that play important roles in
negative growth control, including growth suppression and apoptosis.
MyD118 and Gadd45 are related proteins that previously were shown to
interact with proliferating cell nuclear antigen (PCNA), implicated in
DNA replication, DNA repair, and cell cycle progression. To establish
the role of MyD118 and Gadd45 interactions with PCNA, in this work we
sought to identify the interacting domains and analyze the significance
of this interaction in negative growth control. Using complementary
in vivo and in vitro interaction assays the
N-terminal (1-46) and middle (100-127) regions of PCNA were
identified as harboring MyD118- and Gadd45 interacting domains, whereas
PCNA interacting domains within MyD118 and Gadd45 were localized to the
C termini of these proteins (amino acids 114-156 and 137-165,
respectively). These findings provide first evidence that similar
domains within MyD118 and Gadd45 mediate interactions with PCNA.
Importantly, ectopic expression of MyD118 or Gadd45 N-terminal
peptides, lacking the PCNA interacting domain, was found to suppress
colony formation or induce apoptosis more efficiently than the
full-length proteins. These findings suggest that interaction of MyD118
or Gadd45 with PCNA, in essence, serves to impede negative growth control.
Characterization of MyD118, Gadd45, and Proliferating Cell
Nuclear Antigen (PCNA) Interacting Domains
PCNA IMPEDES MyD118 AND Gadd45-MEDIATED NEGATIVE GROWTH
CONTROL*
, and
*
This research was supported by National Institutes of Health
Grant 1RO1CA43618 (to D. A. L.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence may be addressed: Fels Inst. for Cancer
Research and Molecular Biology and the Dept. of Biochemistry, Temple
University School of Medicine, 3307 N. Broad St.,
Philadelphia, Pennsylvania 19140. Tel.: 215-707-6903/2; Fax:
215-707-2805; E-mail: lieberma@unix.temple.edu or
hoffman@unix.temple.edu.
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