A Role for PML in Innate Immunity | Zendy

Andrea Lunardi | Zendy; Mirella Gáboli | Zendy; Marco Giorgio | Zendy; Roberta Rivi | Zendy; Anne E. Bygrave | Zendy; Michael Antoniou | Zendy; Dubravka Drabek | Zendy; Elaine Dzierzak | Zendy; Matteo Fagioli | Zendy; Leonardo Salmena | Zendy; Marina Botto | Zendy; Carlos CordonCardo | Zendy; Lucio Luzzatto | Zendy; Pier Giuseppe Pelicci | Zendy; Frank Grosveld | Zendy; Pier Paolo Pandolfi | Zendy

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A Role for PML in Innate Immunity

Author(s) -

Andrea Lunardi,

Mirella Gáboli,

Marco Giorgio,

Roberta Rivi,

Anne E. Bygrave,

Michael Antoniou,

Dubravka Drabek,

Elaine Dzierzak,

Matteo Fagioli,

Leonardo Salmena,

Marina Botto,

Carlos CordonCardo,

Lucio Luzzatto,

Pier Giuseppe Pelicci,

Frank Grosveld,

Pier Paolo Pandolfi

Publication year - 2011

Publication title -

genes and cancer

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.883

H-Index - 71

eISSN - 1947-6027

pISSN - 1947-6019

DOI - 10.1177/1947601911402682

Subject(s) - innate immune system , immunology , immune system , biology , chemokine , leukemia , acute promyelocytic leukemia , promyelocytic leukemia protein , acquired immune system , inflammation , lipopolysaccharide , medicine , cancer research , gene , retinoic acid , genetics

The promyelocytic leukemia gene (PML) of acute promyelocytic leukemia is an established tumor suppressor gene with critical functions in growth suppression, induction of apoptosis, and cellular senescence. Interestingly, although less studied, PML seems to play a key role also in immune response to viral infection. Herein, we report that Pml(-/-) mice spontaneously develop an atypical invasive and lethal granulomatous lesion known as botryomycosis (BTM). In Pml(-/-) mice, BTM is the result of impaired function of macrophages, whereby they fail to become activated and are thus unable to clear pathogenic microorganisms. Accordingly, Pml(-/-) mice are resistant to lipopolysaccharide (LPS)-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-κB prosurvival pathway. These results not only shed light on a new fundamental function of PML in innate immunity, but they also point to a proto-oncogenic role for PML in certain cellular and pathological contexts.

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