Entrez Gene

General information | Expression | Regulation | Mutation | Interaction

Basic Information
Gene ID	693123
Name	MIR449B
Synonymous	MIRN449B;microRNA 449b;MIR449B;microRNA 449b
Definition	-
Position	5q11.2
Gene type	miscRNA
Source	Count: 1; Generif
Sentence	Abstract
"Enhanced NPM-retinoblastoma tumor suppressor protein (pRB) interaction, leading to the relief of the repressive pRB-E2F1 circuitry and the consequent transcriptional activation of E2F1 and several downstream DNA repair genes."	Nucleophosmin (NPM) is an important phosphoprotein with pleiotropic functions in various cellular processes. Although phosphorylation has been postulated as an important functional determinant, possible regulatory roles of this modification on NPM are not fully characterized. Here, we find that NPM is dephosphorylated on various threonine residues (Thr199 and Thr234/237) in response to UV-induced DNA damage. Further experiments indicate that the serine/threonine protein phosphatase PP1beta is a physiological NPM phosphatase under both the genotoxic stress and growth conditions. As a consequence, NPM in its hypophosphorylated state facilitates DNA repair. Finally, our results suggest that one possible mechanism of this protective response lies in enhanced NPM-retinoblastoma tumor suppressor protein (pRB) interaction, leading to the relief of the repressive pRB-E2F1 circuitry and the consequent transcriptional activation of E2F1 and several downstream DNA repair genes. Thus, this study unveils a key phosphatase of NPM and highlights a novel mechanism by which the PP1beta-NPM pathway contributes to cellular DNA damage response.
"reveals a tumor suppressor function of miR-449a/b through regulating Rb/E2F1 activity, and suggests that escape from this regulation through an aberrant epigenetic event contributes to E2F1 deregulation and unrestricted proliferation in human cancer"	The Rb-E2F pathway drives cell cycle progression and cell proliferation, and the molecular strategies safeguarding its activity are not fully understood. Here we report that E2F1 directly transactivates miR-449a/b. miR-449a/b targets and inhibits oncogenic CDK6 and CDC25A, resulting in pRb dephosphorylation and cell cycle arrest at G1 phase, revealing a negative feedback regulation of the pRb-E2F1 pathway. Moreover, miR-449a/b expression in cancer cells is epigenetically repressed through histone H3 Lys27 trimethylation, and epigenetic drug treatment targeting histone methylation results in strong induction of miR-449a/b. Our study reveals a tumor suppressor function of miR-449a/b through regulating Rb/E2F1 activity, and suggests that escape from this regulation through an aberrant epigenetic event contributes to E2F1 deregulation and unrestricted proliferation in human cancer.