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2 results on '"Strmiska, Vladislav"'

1. CDC7-independent G1/S transition revealed by targeted protein degradation

Author

Suski, Jan M., Ratnayeke, Nalin, Braun, Marcin, Zhang, Tian, Strmiska, Vladislav, Michowski, Wojciech, Can, Geylani, Simoneau, Antoine, Snioch, Konrad, Cup, Mikolaj, Sullivan, Caitlin M., Wu, Xiaoji, Nowacka, Joanna, Branigan, Timothy B., Pack, Lindsey R., DeCaprio, James A., Geng, Yan, Zou, Lee, Gygi, Steven P., Walter, Johannes C., Meyer, Tobias, and Sicinski, Piotr

Abstract

The entry of mammalian cells into the DNA synthesis phase (S phase) represents a key event in cell division1. According to current models of the cell cycle, the kinase CDC7 constitutes an essential and rate-limiting trigger of DNA replication, acting together with the cyclin-dependent kinase CDK2. Here we show that CDC7 is dispensable for cell division of many different cell types, as determined using chemical genetic systems that enable acute shutdown of CDC7 in cultured cells and in live mice. We demonstrate that another cell cycle kinase, CDK1, is also active during G1/S transition both in cycling cells and in cells exiting quiescence. We show that CDC7 and CDK1 perform functionally redundant roles during G1/S transition, and at least one of these kinases must be present to allow S-phase entry. These observations revise our understanding of cell cycle progression by demonstrating that CDK1 physiologically regulates two distinct transitions during cell division cycle, whereas CDC7 has a redundant function in DNA replication.

Published
2022
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2. Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe‐Dnmts axis.

Author

Strmiska, Vladislav, Michalek, Petr, Lackova, Zuzana, Guran, Roman, Krizkova, Sona, Vanickova, Lucie, Zitka, Ondrej, Stiborova, Marie, Eckschlager, Tomas, Klejdus, Borivoj, Pacik, Dalibor, Tvrdikova, Eliska, Keil, Claudia, Haase, Hajo, Adam, Vojtech, and Heger, Zbynek

Abstract

DNA hypermethylation is one of the most common epigenetic modifications in prostate cancer (PCa). Several studies have delineated sarcosine as a PCa oncometabolite that increases the migration of malignant prostate cells while decreasing their doubling time. Here, we show that incubation of prostate cells with sarcosine elicited the upregulation of sarcosine N‐demethylation enzymes, sarcosine dehydrogenase and pipecolic acid oxidase. This process was accompanied by a considerable increase in the production of the major methyl‐donor S‐adenosylmethionine (SAMe), together with an elevation of cellular methylation potential. Global DNA methylation analyses revealed increases in methylated CpG islands in distinct prostate cell lines incubated with sarcosine, but not in cells of nonprostate origin. This phenomenon was further associated with marked upregulation of DNA methyltransferases (Dnmts). Epigenetic changes were recapitulated through blunting of Dnmts using the hypomethylating agent 5‐azacytidine, which was able to inhibit sarcosine‐induced migration of prostate cells. Moreover, spatial mapping revealed concomitant increases in sarcosine, SAMe and Dnmt1 in histologically confirmed malignant prostate tissue, but not in adjacent or nonmalignant tissue, which is in line with the obtained in vitro data. In summary, we show here for the first time that sarcosine acts as an epigenetic modifier of prostate cells and that this may contribute to its oncometabolic role. [ABSTRACT FROM AUTHOR]

Published
2019
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