Polyamines are organic polycations essential for cell growth and differentiation; their aberrant accumulation is often associated with diseases, including many types of cancer. To maintain polyamine homeostasis, the catalytic activity and protein abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by the regulatory proteins antizyme isoform 1 (Az 1 ) and antizyme inhibitor (AzIN). Az 1 suppresses polyamine production by inhibiting the assembly of the functional ODC homodimer and, most uniquely, by targeting ODC for ubiquitin-independent proteolytic destruction by the 26S proteasome. In contrast, AzIN positively regulates polyamine levels by competing with ODC for Az 1 binding. The structural basis of the Az 1 -mediated regulation of polyamine homeostasis has remained elusive. Here we report crystal structures of human Az 1 complexed with either ODC or AzIN. Structural analysis revealed that Az 1 sterically blocks ODC homodimerization. Moreover, Az 1 binding triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC, which illustrates how a substrate protein may be primed upon association with Az 1 for ubiquitin-independent proteasome recognition. Dynamic and functional analyses further indicated that the Az 1 -induced binding and degradation of ODC by proteasome can be decoupled, with the intrinsically disordered C-terminal tail fragment of ODC being required only for degradation but not binding. Finally, the AzIN-Az 1 structure suggests how AzIN may effectively compete with ODC for Az 1 to restore polyamine production. Taken together, our findings offer structural insights into the Az-mediated regulation of polyamine homeostasis and proteasomal degradation.polyamine homeostasis | ornithine decarboxylase | antizyme | antizyme inhibitor | ubiquitin-independent proteolysis P olyamines are multivalent organic cations that are ubiquitous and essential in eukaryotes (1). With their polycationic characteristics, these compounds are known to modulate the structural and functional properties of nucleic acids and proteins via electrostatic interactions, in turn affecting cell growth and differentiation by influencing the underlying cellular processes (1, 2). Consistent with their crucial regulatory roles, fluctuations in intracellular polyamine levels are rigorously controlled during cell growth and differentiation via fine-tuning the balance between the biosynthesis, degradation, and uptake of polyamines. Aberrant accumulation of polyamines is associated with pathological consequences, including many types of cancer (3-5).Regulation of polyamine homeostasis is achieved mainly by adjusting the catalytic activity and protein abundance of ornithine decarboxylase (ODC), a homodimeric and pyridoxal 5ʹ-phosphatedependent enzyme that catalyzes the committed and rate-limiting step in polyamine biosynthesis, through the actions of the regulatory proteins antizyme isoform 1 (Az 1 ) and antizyme inhibitor (AzIN) (3, 6). E...
Although research suggests that Eastern, collectivist cultures do not benefit as much from practicing gratitude compared to Western, individualist cultures, the reasons for these differences remain unclear. In a single time-point randomized controlled intervention, participants in India (N = 431), Taiwan (N = 112), and the U.S. (N = 307) were randomly assigned either to write a gratitude letter to someone who had done a kind act for them, to write a gratitude letter to themselves for a kind act they had done for another person, or to complete a neutral control writing activity. Immediately after completing their assigned writing activity, participants completed measures of state gratitude, elevation, and emotions (guilt, indebtedness, embarrassment, positive affect, and negative affect). U.S. (but not Indian and Taiwanese) participants who expressed gratitude reported greater state gratitude relative to controls. Although not explicitly grateful, however, Indian and Taiwanese participants who wrote gratitude letters reported higher elevation (and Indian participants, reduced negative affect) compared to control participants. Finally, compared to control participants, Taiwanese (but not U.S.) participants felt less guilty when writing a gratitude letter to themselves. The results provide new insights for why expressing gratitude may be a less effective happiness-promoting activity in collectivist cultures.
This article introduces the Early Childhood Foundations Model for Self-Determination and provides a rationale for the need to consider the foundations of self-determination behavior that begin early in life. This model is based on the premise that young children with disabilities benefit from a collaborative partnership between important adults in the lives of children to provide a supportive, stimulating, and coordinated environment between inclusive classrooms and home settings. Within partnership, the Foundations Model establishes the proposition that the basic foundational skills for developing selfdetermination in later life require young children with disabilities to gain skills in (a) choice-making and problem solving, (b) self-regulation, and (c) engagement. In this position paper, the authors review literature related to these three foundational constructs and present a rationale for use of the Foundations Model as a guide to developing systematic interventions to start young students with disabilities on the road to building a foundation for self-determination.
This article aimed to establish the psychometric properties of the Chinese version of the Subjective Happiness Scale (SHS-C) and to investigate the convergence between SHS-C and multidimensional subjective well-being (MSWB). A total of 543 college students completed the following measures: the SHS-C, the MSWB scale, Rosenberg’s self-esteem scale, and the interpersonal harmony scale. The SHS-C showed adequate internal consistent reliability and test–retest reliability. Confirmatory factor analysis (CFA) showed a one-factor structure of the SHS-C, and multigroup CFA showed factor invariance between gender groups. Subjective happiness, as measured by the SHS-C, and MSWB, as measured by life satisfaction, positive affect, and negative affect, were highly correlated (above .90), suggesting convergent validity. The SHS-C was also correlated with two theoretically different but related constructs, self-esteem and interpersonal harmony, providing evidence of criterion-related validity. The results provide preliminary evidence that the SHS-C is valid with a Chinese-speaking population and that the SHS-C and MSWB may be interchangeable.
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