The deacylase SIRT5 supports melanoma viability by influencing chromatin dynamics.

Cutaneous melanoma remains the most lethal skin cancer, and ranks third among all malignancies in terms of years of life lost. Despite the advent of immune checkpoint and targeted therapies, only roughly half of patients with advanced melanoma achieve a durable remission. Sirtuin 5 (SIRT5) is a member of the sirtuin family of protein deacylases that regulates metabolism and other biological processes. Germline Sirt5 deficiency is associated with mild phenotypes in mice. Here we showed that SIRT5 was required for proliferation and survival across all cutaneous melanoma genotypes tested, as well as uveal melanoma, a genetically distinct melanoma subtype that arises in the eye and is incurable once metastatic. Likewise, SIRT5 was required for efficient tumor formation by melanoma xenografts and in an autochthonous mouse Braf Pten-driven melanoma model. Via metabolite and transcriptomic analyses, we found that SIRT5 was required to maintain histone acetylation and methylation levels in melanoma cells, thereby promoting proper gene expression. SIRT5-dependent genes notably included MITF, a key lineage-specific survival oncogene in melanoma, and the c-MYC proto-oncogene. SIRT5 may represent a druggable genotype-independent addiction in melanoma.

How students choose E-learning resources: The importance of ease, familiarity, and convenience.

Electronic learning resources are popular with today's students. However, how students choose their favorite e-learning resources is not well-understood. The popular SecondLook TM histology self-review tool was offered in three different interfaces to students participating in two histology courses (Cell and Developmental Biology [CDB] 450/550 and DENT 510). These interfaces included PowerPoint files, an online website, and a mobile application (app). Identical in content, each interface had specific advantages and disadvantages with respect to compatible devices, user features, and access limitations. Upon the conclusion of the courses, students were surveyed about their interface preference, reasons for their selection, and general usage of the SecondLook TM resource. With a 91.4% overall survey participation rate, only 3 out of 213 participating students never used the resource. Many students (46.3% CDB 450/550, 62.9% DENT 510) tried only one interface, with PowerPoint being the most popular final choice (56.5% CBD 450/550, 65.7% DENT 510). Although the interactive website and mobile app offered additional user-friendly features, they only garnered between 16% and 24% final popularity. "Convenience," "larger screen," and "easy to use" were most often reported as reasons for students' interface preference. The accessibility of where and when the SecondLook TM resource can be used was also frequently cited. This availability encouraged some students to forgo other learning resources and to use the mobile app in distractive environments. The results of this study suggest that today's students are in fact less motivated to seek out high-tech e-learning resources than commonly believed and instead often select interfaces with which they are already familiar.

Emerging Roles for SIRT5 in Metabolism and Cancer.

SIGNIFICANCE: Developing evidence in the literature suggests that sirtuin 5 (SIRT5) may be involved in metabolic reprogramming, an emerging hallmark of cancer by which neoplastic cells reconfigure their metabolism to support the anabolic demands of rapid cell division. SIRT5 is one of the seven members of the nicotinamide adenine dinucleotide-dependent sirtuin family of lysine deacetylases. It removes succinyl, malonyl, and glutaryl groups from protein targets within the mitochondrial matrix and other subcellular compartments. SIRT5 substrates include a number of proteins integral to metabolism. Recent Advances: New work has begun to elucidate the roles of SIRT5 in glycolysis, tricarboxylic acid cycle, fatty acid oxidation, nitrogen metabolism, pentose phosphate pathway, antioxidant defense, and apoptosis. CRITICAL ISSUES: In this study, we summarize biological functions of SIRT5 reported in normal tissues and in cancer and discuss potential mechanisms whereby SIRT5 may impact tumorigenesis, particularly focusing on its reported roles in metabolic reprogramming. Finally, we review current efforts to target SIRT5 pharmacologically. FUTURE DIRECTIONS: The biological significance of SIRT5 has been elucidated in the context of only an extremely small fraction of its targets and interactors. There is no doubt that further studies in this area will provide a wealth of insights into functions of SIRT5 and its targets in normal and neoplastic cells. Antioxid. Redox Signal. 28, 677-690.