Pregnenolone Functions in Centriole Cohesion during Mitosis

Hamasaki, Mayumi; Matsumura, Shigeki; Satou, Ayaka; Takahashi, Chisato; Oda, Yusuke; Higashiura, Chika; Ishihama, Yasushi; Toyoshima, Fumiko

doi:10.1016/j.chembiol.2014.11.005

Cited by 12 publications

(12 citation statements)

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“…Within the body there are more forces at work than in vitro, including the presence of serum proteins that bind different steroids with different affinities, but our results suggest that cells in the body may accumulate steroids from the bloodstream in a similar manner to cells in a dish from their surrounding culture media. This tendency has not previously been recognized as a general property of cells, but other in vitro [51] and in vivo [34] studies have also shown examples of cells markedly accumulating certain steroids. Our results suggest that this is not just a specific property of certain cells, but rather a broad principle that arises from the physicochemical properties of cells and steroids.…”

Section: Discussionmentioning

confidence: 95%

Rapid and structure-specific cellular uptake of selected steroids

et al. 2019

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Steroid hormones and their respective nuclear receptors are essential mediators in numerous physiologic and pathophysiologic processes, ranging from regulation of metabolism, immune function, and reproductive processes to the development of hormone-dependent cancers such as those of the breast and prostate. Because steroids must enter cells before activating nuclear receptors, understanding the mechanisms by which cellular uptake occurs is critical, yet a clear understanding of these mechanisms has been elusive. It is generally assumed that diffusion-driven uptake is similar across various steroids whereas an elevated cellular concentration is thought to reflect active uptake, but these assumptions have not been directly tested. Here we show that intact cells rapidly accumulate free steroids to markedly elevated concentrations. This effect varies widely depending on steroid structure; more lipophilic steroids reach more elevated concentrations. Strong preferences exist for 3β-OH, Δ5-steroids vs. 3-keto, Δ4-structural features and for progestogens vs. androgens. Surprisingly, steroid-structure-specific preferences do not require cell viability, implying a passive mechanism, and occur across cells derived from multiple tissue types. Physiologic relevance is suggested by structure-specific preferences in human prostate tissue compared with serum. On the other hand, the presence of serum proteins in vitro blocks much, but not all, of the passive accumulation, while still permitting a substantial amount of active accumulation for certain steroids. Our findings suggest that both passive and active uptake mechanisms make important contributions to the cellular steroid uptake process. The role of passive, lipophilicity-driven accumulation has previously been largely unappreciated, and its existence provides important context to studies on steroid transport and action both in vitro and in vivo.

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Section: Discussionmentioning

confidence: 95%

Rapid and structure-specific cellular uptake of selected steroids

et al. 2019

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“…On replacing the native Scc1 with artificially cleavable subunit, the corresponding site‐specific protease triggers centrioles disengagement. A recent study also shows the involvement of shugoshin in centriole protection [Hamasaki et al, ; Mohr et al, ]. Apart from that study also showed the presence of Rad21 at centrosome [Giménez‐Abián et al, ].…”

Section: Separasementioning

confidence: 92%

Separase: Function Beyond Cohesion Cleavage and an Emerging Oncogene

Kumar

2017

J of Cellular Biochemistry

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Proper and timely segregation of genetic endowment is necessary for survival and perpetuation of every species. Mis-segregation of chromosomes and resulting aneuploidy leads to genetic instability, which can jeopardize the survival of an individual or population as a whole. Abnormality with segregation of genetic contents has been associated with several medical consequences including cancer, sterility, mental retardation, spontaneous abortion, miscarriages, and other birth related defects. Separase, by irreversible cleavage of cohesin complex subunit, paves the way for metaphase/anaphase transition during the cell cycle. Both over or reduced expression and altered level of separase have been associated with several medical consequences including cancer, as a result separase now emerges as an important oncogene and potential molecular target for medical intervenes. Recently, separase is also found to be essential in separation and duplication of centrioles. Here, I review the role of separase in mitosis, meiosis, non-canonical roles of separase, separase regulation, as a regulator of centriole disengagement, nonproteolytic roles, diverse substrates, structural insights, and association of separase with cancer. At the ends, I proposed a model which showed that separase is active throughout the cell cycle and there is a mere increase in separase activity during metaphase contrary to the common believes that separase is inactive throughout cell cycle except for metaphase. J. Cell. Biochem. 118: 1283-1299, 2017. © 2016 Wiley Periodicals, Inc.

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“…Similarly, the lipid family of phosphoinositides was shown to directly influence mitotic progression through proteins like NuMA (119) or phosphatases (120) and by regulating cytoskeletal elements (121,122). Sterols have also been shown to play a role in cell division: cells deprived of cholesterol have difficulty undergoing cytokinesis (123), and the cholesterol derivative pregnenolone localizes to the spindle poles, binds Shugoshin 1, and promotes centriole cohesion (124). In S. pombe, intracellular concentrations of glucose affect Wee1 activity and thus cell size at mitotic entry (125).…”

Section: Future Perspectivesmentioning

confidence: 99%

Dissecting the mechanisms of cell division

Ong

Torres

2019

Journal of Biological Chemistry

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Cell division is a highly regulated and carefully orchestrated process. Understanding the mechanisms that promote proper cell division is an important step toward unraveling important questions in cell biology and human health. Early studies seeking to dissect the mechanisms of cell division used classical genetics approaches to identify genes involved in mitosis and deployed biochemical approaches to isolate and identify proteins critical for cell division. These studies underscored that post-translational modifications and cyclin-kinase complexes play roles at the heart of the cell division program. Modern approaches for examining the mechanisms of cell division, including the use of high-throughput methods to study the effects of RNAi, cDNA, and chemical libraries, have evolved to encompass a larger biological and chemical space. Here, we outline some of the classical studies that established a foundation for the field and provide an overview of recent approaches that have advanced the study of cell division.

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Pregnenolone Functions in Centriole Cohesion during Mitosis

Cited by 12 publications

References 50 publications

Rapid and structure-specific cellular uptake of selected steroids

Rapid and structure-specific cellular uptake of selected steroids

Separase: Function Beyond Cohesion Cleavage and an Emerging Oncogene

Dissecting the mechanisms of cell division

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