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Thomas M. Yung

Bio: Thomas M. Yung is an academic researcher from Memorial Sloan Kettering Cancer Center. The author has contributed to research in topics: Promyelocytic leukemia protein & Phosphorylation. The author has an hindex of 5, co-authored 7 publications receiving 936 citations.

Papers
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Journal ArticleDOI
TL;DR: It is demonstrated that PML contains a SUMO binding motif that is independent of its SUMOylation sites and is surprisingly necessary for PML-NB formation, and it is proposed that the PML RING domain is critical forPML SUMoylation and PML -NB formation.

475 citations

Journal ArticleDOI
28 Jul 2006-Cell
TL;DR: It is shown that CK2 regulates PML protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at Ser517, Consequently, PML mutants that are resistant to CK2 phosphorylated display increased tumor-suppressive functions.

285 citations

Journal ArticleDOI
TL;DR: It is demonstrated that PML contains a SUMO binding motif that is independent of its SUMOylation sites and is surprisingly necessary for PML-NB formation, and it is proposed that the PML RING domain is critical forPML SUMoylation and PMLNB formation.

143 citations

Journal ArticleDOI
TL;DR: The findings that PML undergoes ubiquitin/proteasome-mediated degradation in immortalized and tumor derived cell lines are reviewed and suggest that CK2 inhibitors may be beneficial anti-cancer drugs.
Abstract: The PML tumor suppressor controls growth suppression, induction of apoptosis, and cellular senescence. PML loss occurs frequently in hematopoietic and solid tumors. PML loss often correlates with tumor progression. Casein kinase 2 (CK2) is a stress-activated serine/threonine protein kinase that is oncogenic and frequently overexpressed in human tumor of multiple histological origins. In addition, CK2 overexpression due to gene amplification has been reported to be an adverse prognostic factor in non-small cell lung cancer. At the 5th International Conference on Protein Kinase CK2 in Padova, Italy, we reviewed our recent findings that PML undergoes ubiquitin/proteasome-mediated degradation in immortalized and tumor derived cell lines. PML degradation depends on direct CK2 phosphorylation of PML Ser517. PML mutants that are resistant to CK2 phosphorylation display increased tumor suppressive functions in assays measuring apoptosis, replicative senescence, and in xenograft models. More significantly, CK2 pharmacological inhibition enhances PML tumor suppressive property. These data identify a key post-translational mechanism that controls PML protein levels in cancer cells and suggest that CK2 inhibitors may be beneficial anti-cancer drugs.

54 citations

Journal ArticleDOI
TL;DR: It is demonstrated that upregulation of PML translation plays a central role in oncogenic K‐RAS‐induced OIS and that selective translation initiation plays a critical role in tumour suppression with important therapeutic implications for the treatment of solid tumours and APL.
Abstract: Expression of oncogenic K‐RAS in primary cells elicits oncogene‐induced cellular senescence (OIS), a form of growth arrest that potently opposes tumourigenesis. This effect has been largely attributed to transcriptional mechanisms that depend on the p53 tumour suppressor protein. The PML tumour suppressor was initially identified as a component of the PML‐RARα oncoprotein of acute promyelocytic leukaemia (APL). PML, a critical OIS mediator, is upregulated by oncogenic K‐RAS in vivo and in vitro . We demonstrate here that oncogenic K‐RAS induces PML protein upregulation by activating the RAS/MEK1/mTOR/eIF4E pathway even in the absence of p53. Under these circumstances, PML mRNA is selectively associated to polysomes. Importantly, we find that the PML 5′ untranslated mRNA region plays a key role in mediating PML protein upregulation and that its presence is essential for an efficient OIS response. These findings demonstrate that upregulation of PML translation plays a central role in oncogenic K‐RAS‐induced OIS. Thus, selective translation initiation plays a critical role in tumour suppression with important therapeutic implications for the treatment of solid tumours and APL.

33 citations


Cited by
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Journal ArticleDOI
TL;DR: A decade has passed since SUMO was discovered to be a reversible post-translational protein modifier and many enzymes that participate in regulated SUMO-conjugation and -deconjugation pathways have been identified and characterized.
Abstract: A decade has passed since SUMO (small ubiquitin-related modifier) was discovered to be a reversible post-translational protein modifier. During this time many enzymes that participate in regulated SUMO-conjugation and -deconjugation pathways have been identified and characterized. In parallel, the search for SUMO substrates has produced a long list of targets, which appear to be involved in most cellular functions. Sumoylation is a highly dynamic process and its outcomes are extremely diverse, ranging from changes in localization to altered activity and, in some cases, stability of the modified protein. At first glance, these effects have nothing in common; however, it seems that they all result from changes in the molecular interactions of the sumoylated proteins.

1,663 citations

Journal ArticleDOI
TL;DR: A combination of techniques from cell biology, biophysics, physical chemistry, structural biology, and bioinformatics are starting to help establish the molecular principles of an emerging field, thus paving the way for exciting discoveries, including novel therapeutic approaches for the treatment of age-related disorders.

1,317 citations

Journal ArticleDOI
TL;DR: Recent data are described that reveal broader antiviral and antimicrobial activities of TRIM proteins and their involvement in the regulation of pathogen-recognition and transcriptional pathways in host defence is discussed.
Abstract: The superfamily of tripartite motif-containing (TRIM) proteins is conserved throughout the metazoan kingdom and has expanded rapidly during vertebrate evolution; there are now more than 60 TRIM proteins known in humans and mice. Many TRIM proteins are induced by type I and type II interferons, which are crucial for many aspects of resistance to pathogens, and several are known to be required for the restriction of infection by lentiviruses. In this Review, we describe recent data that reveal broader antiviral and antimicrobial activities of TRIM proteins and discuss their involvement in the regulation of pathogen-recognition and transcriptional pathways in host defence.

897 citations

Journal ArticleDOI
TL;DR: The promyelocytic leukaemia tumour suppressor protein epitomizes the PML-nuclear body (PML-NB) and is crucially required for the proper assembly of this macromolecular nuclear structure.
Abstract: The promyelocytic leukaemia (PML) tumour suppressor protein epitomizes the PML-nuclear body (PML-NB) and is crucially required for the proper assembly of this macromolecular nuclear structure. Unlike other, more specialized subnuclear structures such as Cajal and Polycomb group bodies, PML-NBs are functionally promiscuous and have been implicated in the regulation of diverse cellular functions. PML-NBs are dynamic structures that favour the sequestration and release of proteins, mediate their post-translational modifications and promote specific nuclear events in response to various cellular stresses. Recent data suggest that PML-NBs may be heterogeneous in composition, mobility and function.

864 citations

Journal ArticleDOI
28 Jul 2016-Cell
TL;DR: The data suggest a conceptual framework for considering the composition and control of cellular bodies assembled through heterotypic multivalent interactions, suggesting how their compositions could be controlled by levels of PML SUMOylation or cellular mRNA concentration, respectively.

854 citations