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Vertiz, J.

Publications and source records attributed to Vertiz, J..

2 recordsLinked to original sources

A meiotic B-type cyclin selectively drives mitotic progression and fidelity in cancer cells

Cell cycle transitions are driven by cyclins in complex with cyclin-dependent kinases (CDK). Here, we demonstrate that cyclin B3, an evolutionarily divergent B-type cyclin previously thought to function exclusively in female meiosis, is expressed in mitotic cells and interacts with both CDK1 and CDK2. We show that cyclin B3-CDK1/2 is essential for timely mitotic progression by ensuring proper chromosome alignment and stable kinetochore-microtubule interactions, while its overexpression accelerates mitosis and improves chromosome alignment kinetics. Through phospho-mass spectrometry, we identify several kinetochore and mitotic spindle components as substrates of cyclin B3-CDK1/2 in mitosis. Notably, cyclin B3 depletion disrupts mitotic progression in most cancer cell lines tested - including colorectal, osteosarcoma, and breast cancer models - while non-transformed cells are largely unaffected. These findings identify cyclin B3-CDK1/2 as a novel driver of mitotic progression and reveal a preferential dependency in a subset of cancer cells that may represent a potential therapeutic vulnerability.

cancer biology↗

The Regulation of Developmental Diapause is Coordinated with Molting and Olfaction

Developmental and behavioral plasticity allow animals to prioritize alternative genetic programs during fluctuating environments. Behavioral remodeling may be acute in animals that interact with host organisms, since reproductive adults and the developmentally arrested larvae often have different ethological needs for chemical stimuli. To understand the genes that coordinate development and behavior, we used the nematode model Pristionchus pacificus to characterize mutants that inappropriately enter developmental diapause to become dauer larvae (Daf-c). We found several key olfactory differences between P. pacificus and C. elegans Daf-c dauers. In addition, the two P. pacificus Daf-c alleles disrupt steroid synthesis required for proper regulation of the conserved canonical steroid hormone receptor DAF-12, whose dauer-constitutive and cuticle exsheathment phenotypes can be rescued by the feeding of {Delta}7-dafachronic acid. One allele, csu60, has a deletion in the sole HydroxySteroid Dehydrogenase (HSD) in P. pacificus. Both hsd-2(csu60) adults and dauers show enhanced attraction to a beetle pheromone, possibly due to the heterochronic activation of dauer-specific neuronal development in the adults. Surprisingly, this enhanced odor attraction acts independently of daf-12, revealing unexpected targets of steroid hormones regulating ecdysis and olfaction in P. pacificus. Author SummaryThe remarkable evolutionary success of nematodes can be attributed to their dispersal ability as stress-resistant dauer larvae and the equivalent parasitic infective larvae. The decision to enter dauer development is regulated by a conserved steroid hormone receptor that receives multiple external and internal cues, though the extent in which these cues also coordinate other physiological and behavioral processes is not well understood in divergent species. We used the insect-associated nematode Pristionchus pacificus to genetically dissect two mutants that form dauers inappropriately, and found that one mutation in a steroidogenic enzyme, Ppa-hsd-2, is predicted to abolish the biosynthesis of the hormones needed to negatively regulate dauer entry when food is available. Unexpectedly, Ppa-HSD-2 is also required to properly complete the dauer larval molt, known as exsheathment, as well as to confer differences in adult versus dauer larvae chemotaxis behavior towards a host pheromone. Given that dauers are the host-seeking stage of parasitic nematodes, hormonal disruption represents a tenable target for biological control.

developmental biology↗