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  • Herein we report the expression of shrimp Cdk in hepatopancr

    2020-05-29

    Herein we report the expression of shrimp Cdk-2 in hepatopancreas, gills and muscle, finding higher expression in hepatopancreas and gills and lower expression in muscle. No significant changes due to hypoxia and hypoxia reoxygenation were detected on the expression of Cdk-2 in hepatopancreas and gills, but since Cdk-2 expression is higher in these tissues than in muscle, this suggests HyperScribe Poly (A) Tailing Kit progression remains in these tissues. However, in muscle the expression of LvCdk-2 was up-regulated in shrimps that were subjected to hypoxic treatments, returning to similar levels of those found in normoxia in hypoxia-reoxygenation. In ovarian carcinoma cells, hypoxia causes reversible cell cycle arrest through hypophosphorylation of the Rb protein and after reoxygenation, cells continued with cell cycle progression (Krtolica and Ludlow, 1996). Cdk/Cyclin complexes can be subjected to different types of regulation, like phosphorylation of inhibitory sites such as the glycine-rich region located in the N-terminal HyperScribe Poly (A) Tailing Kit lobe as well as binding of Cdk inhibitors of the CIP/KIP class, as the p21 protein. The p21 protein is the main effector regulated by the p53 protein in response to stress in vertebrates. This protein can inhibit the Cdk/Cyclin complex by blocking their interaction with substrates or the CAK (Xiong et al., 1993; Nigg, 1995; Russo et al., 1996) and its role in cell arrest in the G1 phase has been demonstrated (Wang et al., 1999; Arima et al., 2004). We previously reported that in hepatopancreas of shrimps that were subjected to p53 silencing and afterwards to hypoxia, an increase in the expression of Cdk-2 after 48 h of hypoxia occurs, suggesting that in shrimp, p53 induces the activation of Rb via p21 which results in Cdk-2 transcripts repression (Nuñez-Hernandez et al., 2018). In summary, the results herein presented, show that shrimp Cdk-2 is a very highly conserved protein and that its gene is expressed during hypoxia and reoxygenation; where hypoxia induced Cdk-2 expression occurs in muscle. Future studies are necessary to find other proteins that interact with Cdk-2 and gain deeper knowledge of the cellular responses to the stress of hypoxia.
    Author contributions
    Competing interests
    Funding This study was funded by the National Science and Technology Council, Mexico (CONACyT).
    Acknowledgments To CONACyT for funding this work, grants 221240 and A1-S-24557 to GYP. We thank Biol. Adrian Gamez-Alejo, Dr. Silvia Gomez-Jimenez and the personnel from the laboratory of Marine Invertebrates Physiology of CIAD for the technical help provided in the hypoxia bioassay and Dr. Humberto González-Ríos for the help with statistical analysis of the data. DMNH had a CONACYT scholarship for Ph.D. studies at CIAD.
    Introduction According to WHO report (2017), cancer is the second leading cause of death with every 1 in 6 deaths and about 8.8 million deaths in 2015 alone were attributed to cancer [1]. This trend is expected to rise in the coming decades causing significant social and economic burden on the health care system [2]. However, over the past two decades, there has been a greater understanding of cancer at the molecular level leading to significant advancement in diagnosis, management, and treatment of cancer [3,4]. Since chemotherapy remains one of the most effective and common routes for cancer therapy but is also associated with severe toxicity and poor tolerance [5]. Thus, there has been a constant ever-increasing effort by the researchers and pharmaceutical industries to identify and develop target-specific cancer chemotherapeutics for an effective treatment with reduced side effects. Protein kinases are important molecular drug targets for developing novel anticancer agents and several kinase inhibitors are in clinical trials (Fig. 1) [6]. Cyclin-dependent kinases (CDKs) are serine/threonine kinase proteins comprising of 20 members that fall under protein kinases family. These enzymes play a crucial role in cell division, transcription and post-transcriptional modification [7]. For example, the formation of an active complex composed of CDK2 and cyclin E enables pRb phosphorylation, activation of transcription factors E2F that initiates S phase of the cell cycle [8]. CDK2 further associates with cyclin A, governing continuous DNA replication and properly programmed deactivation of E2F. Thus, CDK2 has become a prospective drug target for the treatment of tumours [9]. To date, many CDK2 inhibitors have been developed and some of them (roscovitine, CYC065, dinaciclib, AT7519, milciclib) are under clinical evaluation [10,11]. CDK2 inhibitor proved as a therapeutic target in ovarian cancer [12], neuroblastoma [13] and BRCA-deficient cancers [14]. In addition, a recent research study evidenced that both phosphatidylinositol-3-kinase and CDK2 inhibitors together induced apoptosis in malignant glioma xenografts via a synthetic-lethal interaction [15]