Author
Tian Huai Shen
Bio: Tian Huai Shen is an academic researcher from Memorial Sloan Kettering Cancer Center. The author has contributed to research in topics: Promyelocytic leukemia protein & SUMO protein. The author has an hindex of 2, co-authored 2 publications receiving 576 citations.
Papers
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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
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
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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
Katholieke Universiteit Leuven1, Stanford University2, Max Planck Society3, Brown University4, St. Jude Children's Research Hospital5, University of Zurich6, Switch7, University of Pennsylvania8, Boston University9, Vrije Universiteit Brussel10, Hungarian Academy of Sciences11, University of Debrecen12
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
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
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
TL;DR: PML is identified as the first protein degraded by SUMO-dependent polyubiquitination, as it recruits not only RNF4, ubiquitin and proteasomes, but also many SUMOylated proteins onto PML nuclear bodies, which could physically integrate thesumOylation, ubiquItination and degradation pathways.
Abstract: In acute promyelocytic leukaemia (APL), arsenic trioxide induces degradation of the fusion protein encoded by the PML-RARA oncogene, differentiation of leukaemic cells and produces clinical remissions. SUMOylation of its PML moiety was previously implicated, but the nature of the degradation pathway involved and the role of PML-RARalpha catabolism in the response to therapy have both remained elusive. Here, we demonstrate that arsenic-induced PML SUMOylation triggers its Lys 48-linked polyubiquitination and proteasome-dependent degradation. When exposed to arsenic, SUMOylated PML recruits RNF4, the human orthologue of the yeast SUMO-dependent E3 ubiquitin-ligase, as well as ubiquitin and proteasomes onto PML nuclear bodies. Arsenic-induced differentiation is impaired in cells transformed by a non-degradable PML-RARalpha SUMOylation mutant or in APL cells transduced with a dominant-negative RNF4, directly implicating PML-RARalpha catabolism in the therapeutic response. We thus identify PML as the first protein degraded by SUMO-dependent polyubiquitination. As PML SUMOylation recruits not only RNF4, ubiquitin and proteasomes, but also many SUMOylated proteins onto PML nuclear bodies, these domains could physically integrate the SUMOylation, ubiquitination and degradation pathways.
680 citations