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Post-translational modifications of PML: consequences and implications.

Cheng X, Kao HY - Front Oncol (2013)

Bottom Line: The tumor suppressor promyelocytic leukemia protein (PML) predominantly resides in a structurally distinct sub-nuclear domain called PML nuclear bodies.Post-translational modifications, such as SUMOylation, phosphorylation, acetylation, and ubiquitination of PML add a complex layer of regulation to the physiological function of PML.In this review, we discuss the fast-moving horizon of post-translational modifications targeting PML.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Medicine, Case Western Reserve University Cleveland, OH, USA ; Comprehensive Cancer Center, Case Western Reserve University Cleveland, OH, USA ; University Hospital of Cleveland, Case Western Reserve University Cleveland, OH, USA.

ABSTRACT
The tumor suppressor promyelocytic leukemia protein (PML) predominantly resides in a structurally distinct sub-nuclear domain called PML nuclear bodies. Emerging evidences indicated that PML actively participates in many aspects of cellular processes, but the molecular mechanisms underlying PML regulation in response to stress and environmental cues are not complete. Post-translational modifications, such as SUMOylation, phosphorylation, acetylation, and ubiquitination of PML add a complex layer of regulation to the physiological function of PML. In this review, we discuss the fast-moving horizon of post-translational modifications targeting PML.

No MeSH data available.


Related in: MedlinePlus

Site-specific kinases, SUMO E3 and deconjugating enzymes that target PML. The diagram depicts the modified residues in PML targeted by kinases, SUMO E3 ligases, or SUMO deconjugating enzyme. Arrows indicate the targeting site(s) of these enzymes. Poly-SUMO chains are observed at K160, K380, K400, K490, and K497 and tentatively at K226 and K616. K65 is modified by either SUMO1 or a poly-SUMO chain. The functional consequences of these post-translational modifications are annotated adjacent to the corresponding enzyme.
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Figure 3: Site-specific kinases, SUMO E3 and deconjugating enzymes that target PML. The diagram depicts the modified residues in PML targeted by kinases, SUMO E3 ligases, or SUMO deconjugating enzyme. Arrows indicate the targeting site(s) of these enzymes. Poly-SUMO chains are observed at K160, K380, K400, K490, and K497 and tentatively at K226 and K616. K65 is modified by either SUMO1 or a poly-SUMO chain. The functional consequences of these post-translational modifications are annotated adjacent to the corresponding enzyme.

Mentions: SUMO1 was initially identified as a PML interacting protein through a yeast-two hybrid screen (Boddy et al., 1996). This interaction requires a SUMO-interacting motif (SIM) at the C-terminus of PML (Lin et al., 2006; Shen et al., 2006). A body of evidence has demonstrated that PML is post-translationally conjugated to SUMO1 (Sternsdorf et al., 1997; Kamitani et al., 1998b; Muller et al., 1998) and SUMO2/3 (Kamitani et al., 1998b). Initial studies identified three canonical SUMOylation sites K65, K160, and K490 (Kamitani et al., 1998a) on PML. Additionally, later studies also suggested potential poly-SUMO conjugation sites at K226 and K616 (Vertegaal et al., 2006) and identified three poly-SUMO conjugation sites including K380, K400, and K497 in response to arsenic trioxide treatment (Galisson et al., 2011; Figure 3). By immunofluorescence microscopy, endogenous PML, and SUMO1 were found colocalized in PML NBs (Muller et al., 1998; Gao et al., 2008a). PML NBs are thought to be a nuclear depot where SUMOylation elicits its various roles through modulating PML or components of PML NBs.


Post-translational modifications of PML: consequences and implications.

Cheng X, Kao HY - Front Oncol (2013)

Site-specific kinases, SUMO E3 and deconjugating enzymes that target PML. The diagram depicts the modified residues in PML targeted by kinases, SUMO E3 ligases, or SUMO deconjugating enzyme. Arrows indicate the targeting site(s) of these enzymes. Poly-SUMO chains are observed at K160, K380, K400, K490, and K497 and tentatively at K226 and K616. K65 is modified by either SUMO1 or a poly-SUMO chain. The functional consequences of these post-translational modifications are annotated adjacent to the corresponding enzyme.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3539660&req=5

Figure 3: Site-specific kinases, SUMO E3 and deconjugating enzymes that target PML. The diagram depicts the modified residues in PML targeted by kinases, SUMO E3 ligases, or SUMO deconjugating enzyme. Arrows indicate the targeting site(s) of these enzymes. Poly-SUMO chains are observed at K160, K380, K400, K490, and K497 and tentatively at K226 and K616. K65 is modified by either SUMO1 or a poly-SUMO chain. The functional consequences of these post-translational modifications are annotated adjacent to the corresponding enzyme.
Mentions: SUMO1 was initially identified as a PML interacting protein through a yeast-two hybrid screen (Boddy et al., 1996). This interaction requires a SUMO-interacting motif (SIM) at the C-terminus of PML (Lin et al., 2006; Shen et al., 2006). A body of evidence has demonstrated that PML is post-translationally conjugated to SUMO1 (Sternsdorf et al., 1997; Kamitani et al., 1998b; Muller et al., 1998) and SUMO2/3 (Kamitani et al., 1998b). Initial studies identified three canonical SUMOylation sites K65, K160, and K490 (Kamitani et al., 1998a) on PML. Additionally, later studies also suggested potential poly-SUMO conjugation sites at K226 and K616 (Vertegaal et al., 2006) and identified three poly-SUMO conjugation sites including K380, K400, and K497 in response to arsenic trioxide treatment (Galisson et al., 2011; Figure 3). By immunofluorescence microscopy, endogenous PML, and SUMO1 were found colocalized in PML NBs (Muller et al., 1998; Gao et al., 2008a). PML NBs are thought to be a nuclear depot where SUMOylation elicits its various roles through modulating PML or components of PML NBs.

Bottom Line: The tumor suppressor promyelocytic leukemia protein (PML) predominantly resides in a structurally distinct sub-nuclear domain called PML nuclear bodies.Post-translational modifications, such as SUMOylation, phosphorylation, acetylation, and ubiquitination of PML add a complex layer of regulation to the physiological function of PML.In this review, we discuss the fast-moving horizon of post-translational modifications targeting PML.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Medicine, Case Western Reserve University Cleveland, OH, USA ; Comprehensive Cancer Center, Case Western Reserve University Cleveland, OH, USA ; University Hospital of Cleveland, Case Western Reserve University Cleveland, OH, USA.

ABSTRACT
The tumor suppressor promyelocytic leukemia protein (PML) predominantly resides in a structurally distinct sub-nuclear domain called PML nuclear bodies. Emerging evidences indicated that PML actively participates in many aspects of cellular processes, but the molecular mechanisms underlying PML regulation in response to stress and environmental cues are not complete. Post-translational modifications, such as SUMOylation, phosphorylation, acetylation, and ubiquitination of PML add a complex layer of regulation to the physiological function of PML. In this review, we discuss the fast-moving horizon of post-translational modifications targeting PML.

No MeSH data available.


Related in: MedlinePlus