Murine gammaherpesvirus 68 ORF75c contains ubiquitin E3 ligase activity and requires PML SUMOylation but not other known cellular PML regulators, CK2 and E6AP, to mediate PML degradation
                    
                        
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                    چکیده
منابع مشابه
Murine gammaherpesvirus 68 encodes a second PML-modifying protein.
The ORF75c tegument protein of murine gammaherpesvirus 68 (MHV68) promotes the degradation of the antiviral promyelocytic leukemia (PML) protein. Surprisingly, MHV68 expressing a degradation-deficient ORF75c replicated in cell culture and in mice similar to the wild-type virus. However, in cells infected with this mutant virus, PML formed novel track-like structures that are induced by ORF61, t...
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The promyelocytic leukemia tumor suppressor gene (PML) critically regulates several cellular functions that oppose tumorigenesis such as oncogene-induced senescence, apoptosis, the response to DNA damage and to viral infections. PML deficiency occurs commonly in a broad spectrum of human cancers through mechanisms that involve its aberrant ubiquitination and degradation. Furthermore, several vi...
متن کاملPML, SUMOylation, and Senescence
Since its discovery, 25 years ago, promyelocytic leukemia (PML) has been an enigma. Implicated in the oncogenic PML/RARA fusion, forming elusive intranuclear domains, triggering cell death or senescence, controlled by and perhaps controlling SUMOylation… there are multiple PML-related issues. Here we review the reciprocal interactions between PML, senescence, and SUMOylation, notably in the con...
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Arsenic trioxide (As2O3) is one of the most effective therapeutic agents used for patients with acute promyelocytic leukemia (APL). The probable explanation for As2O3-induced cell differentiation is the direct targeting of PML-RARα oncoprotein by As2O3, which results in initiation of PML-RARα degradation. However, after injection, As2O3 is rapidly methylated in body to different intermediate me...
متن کاملThe SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its oncogenic counterpart PML-RARA.
The ubiquitin-like SUMO proteins covalently modify protein substrates and regulate their functional properties. In a broad spectrum of cancers, the tumor suppressor PML undergoes ubiquitin-mediated degradation primed by CK2 phosphorylation. Here, we report that the SUMO E3-ligase inhibitor PIAS1 regulates oncogenic signaling through its ability to sumoylate PML and the PML-RARA oncoprotein of a...
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ژورنال
عنوان ژورنال: Virology
سال: 2013
ISSN: 0042-6822
DOI: 10.1016/j.virol.2013.02.014