The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for the deposition of N6-methyladenosine (m6A) into mRNAs, containing the METTL3 methyltransferase. However, it is not clear if WTAP may have m6A-independent regulatory functions that might contribute to its oncogenic role. Here, we show that both knockdown and overexpression of METTL3 protein results in WTAP protein upregulation, indicating that METTL3 levels are critical for WTAP protein homeostasis. However, we show that WTAP upregulation is not sufficient to promote cell proliferation in the absence of a functional METTL3. Therein, these data indicate that the reported oncogenic function of WTAP is strictly connected to a functional m6A methylation complex.

METTL3 regulates WTAP protein homeostasis / Sorci, Melissa; Ianniello, Zaira; Cruciani, Sonia; Larivera, Simone; Ginistrelli, Lavinia Ceci; Capuano, Ernestina; Marchioni, Marcella; Fazi, Francesco; Fatica, Alessandro. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - STAMPA. - 9:9(2018). [10.1038/s41419-018-0843-z]

METTL3 regulates WTAP protein homeostasis

Sorci, Melissa
Primo
;
Ianniello, Zaira
Secondo
;
Cruciani, Sonia;Larivera, Simone;Capuano, Ernestina;Fazi, Francesco
Penultimo
;
Fatica, Alessandro
Ultimo
2018

Abstract

The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for the deposition of N6-methyladenosine (m6A) into mRNAs, containing the METTL3 methyltransferase. However, it is not clear if WTAP may have m6A-independent regulatory functions that might contribute to its oncogenic role. Here, we show that both knockdown and overexpression of METTL3 protein results in WTAP protein upregulation, indicating that METTL3 levels are critical for WTAP protein homeostasis. However, we show that WTAP upregulation is not sufficient to promote cell proliferation in the absence of a functional METTL3. Therein, these data indicate that the reported oncogenic function of WTAP is strictly connected to a functional m6A methylation complex.
2018
AML, RNA, METTL3
01 Pubblicazione su rivista::01a Articolo in rivista
METTL3 regulates WTAP protein homeostasis / Sorci, Melissa; Ianniello, Zaira; Cruciani, Sonia; Larivera, Simone; Ginistrelli, Lavinia Ceci; Capuano, Ernestina; Marchioni, Marcella; Fazi, Francesco; Fatica, Alessandro. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - STAMPA. - 9:9(2018). [10.1038/s41419-018-0843-z]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1131988
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