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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN Imprimir: 0893-9675
ISSN On-line: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v16.i1-2.120
pages 129-140

Gadd45 Stress Sensors in Malignancy and Leukemia

Dan Liebermann
1Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, Pennsylvania
Jennifer S. Tront
Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, Pennsylvania
Xiogen Sha
Department of Biochemistry, Temple University, Philadelphia, Pennsylvania
Ksushiki Mukherjee
Department of Biochemistry, Temple University, Philadelphia, Pennsylvania
Alisha Mohamed-Hadley
Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, Pennsylvania
Barbara Hoffman
Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, Pennsylvania;Department of Biochemistry, Temple University, Philadelphia, Pennsylvania

RESUMO

Gadd45 proteins, including Gadd45a, Gadd45b, and Gadd45g, have been implicated in stress signaling in response to physiological and environmental stress, including oncogenic stress, which can result in cell cycle arrest, DNA repair, cell survival, senescence, and apoptosis. The function of Gadd45 as a stress sensor is mediated via a complex interplay of physical interactions with other cellular proteins implicated in cell cycle regulation and the response of cells to stress, notably PCNA, p21, cdc2/cyclinB1, and the p38 and JNK stress response kinases. Altered expression of Gadd45 has been observed in multiple types of solid tumors as well as in hematopoietic malignancies. Using genetically engineered mouse models and bone-marrow transplantation, evidence has been obtained indicating that Gadd45 proteins can function to either promote or suppress tumor development and leukemia; this is dependent on the molecular nature of the activated oncogene and the cell type, via engagement of different signaling pathways.

Palavras-chave: Gadd45, cancer, leukemia

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