NR4A1 (Nur77) belongs together with NR4A2 (Nurr1) and NR4A3 (NOR-1) to the nuclear orphan
receptors of the NR4A-family. Their activation is generally short lived, the cellular outcome is a
stimulus- and cell context-dependent differential activation of NR4A target genes that regulate cell cycle,
apoptosis, inflammation, atherogenesis, metabolism, DNA repair and tumorigenesis. NR4A1 and NR4A3
were identified to function as tumor suppressors in acute myeloid leukemia (AML). Deletion of both nuclear
receptors led to rapid development of AML in mice. Loss of NR4A1 and NR4A3 was a common feature
in human AML patients. Additionally, NR4A1 and NR4A3 hypoallelic mice - mice with a reduced NR4A1 and
NR4A3 expression - develop a chronic myeloid malignancy that recapitulates the pathological features of myelodysplastic/
myeloproliferative neoplasms with progression to AML in rare cases. Recently, a reduced NR4A1 and NR4A3 expression
was described in aggressive lymphomas and low NR4A1 expression was associated with poor overall survival. Overexpression
of NR4A1 in aggressive lymphoma cells led to induction of apoptosis and abrogated tumor growth in a
xenograft mouse model. Recently, it was shown that NR4A inducing agents or NR4A agonist possess/induce apoptotic effects
in AML and lymphoma cells. Due to this fact and the growing number of NR4A1 and NR4A3 inducing agents and
NR4A agonists, both receptors represent new targets for anti tumor therapy.
Keywords: AML, apoptosis, cell cycle arrest, lymphoma, NR4A, therapeutic target, tumor suppressor.
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