Recently, cyclin-dependent kinase (CDK) 4/6 inhibitors have been widely used to treat advanced hormone receptor-positive breast cancer. Despite promising clinical outcomes, almost all patients eventually acquire resistance CDK4/6 inhibitors. Here, we screened genes associated with palbociclib through genomics and transcriptomics in preclinical cancer models. Palbociclib-resistant cells were gen...

Objective: Cyclin D1 is an essential protein that acts as a mitogenic sensor. In this manuscript, we discuss the importance of cyclin in oncology and cardio-oncology, challenge prognostic therapeutic response values to figure out if it can be beneficial marker. We also agents microRNAs used potential approach via regulating expression cardio-oncology. Discussion: Clinical significance defined n...

Mesangial cell (MC) mitogenesis is regulated through "negative cross talk" between cAMP-PKA and ERK signaling. Although it is widely accepted that cAMP inhibits mitogenesis through PKA-mediated phosphorylation of Raf-1, recent studies have indicated that cAMP-mediated inhibition of mitogenesis may occur independently of Raf-1 phosphorylation or without inhibiting ERK activity. We previously sho...

The cyclin-dependent kinase 2 (cdk2) is a serine/threonine protein kinase that plays a key role in the cell cycle control system of all eukaryotic organisms. It has been a much studied drug target for potential anticancer therapy. Most cdk2 inhibitors in clinical development target almost exclusively the catalytic ATP-binding pocket of cdk2. However, several five amino-acid peptide inhibitors t...

The histone deacetylase (HDAC) inhibitors, butyrate and trichostatin A (TSA), are epigenetic histone modifiers and proliferation inhibitors by downregulating cyclin D1, a positive cell cycle regulator, and upregulating p21Cip1 and INK family of proteins, negative cell cycle regulators. Our recent study indicated cyclin D1 upregulation in vascular smooth muscle cells (VSMC) that are proliferatio...

Background: Mammalian cell division is regulated by a complex includes cyclin-dependent kinases (Cdks) and cyclins, Cdk/cyclin complex. The activity of the complex is regulated by Cdk inhibitors (CKIs) compressing CDK4 (INK4) and CDK-interacting protein/kinase inhibitory protein (CIP/KIP) family. Hypermethylation of CKIs has been reported in various cancers. DNA methyltransferase inhibitors (DN...

Cancer treatment often tends to involve direct targeting enzymes essential for the growth and proliferation of cancer cells. The aim of this study was the recognition of the possible role of selected protein kinases: PI3K, ERK1/2, and mTOR in cell proliferation and cell cycle in malignant melanoma. We investigated the role of protein kinase inhibitors: U0126 (ERK1/2), LY294002 (PI3K), rapamycin...

We have previously shown that caspase-mediated cleavage of Cyclin E generates p18-Cyclin E in hematopoietic tumor cells. Its expression can induce apoptosis or sensitize to apoptotic stimuli in many cell types. However, p18-cyclin E has a much shorter half-life than Cyclin E, being more effectively ubiquitinated and degraded by the 26 S proteasome. A two-step process has emerged that regulates ...

To study the regulation of cyclin-dependent kinase (CDK) activity during mitotic exit in mammalian cells, we constructed murine cell lines that constitutively express a stabilized mutant of cyclin A (cyclin A47). Even though cyclin A47 was expressed throughout mitosis and in G1 cells, its associated CDK activity was inactivated after the transition from metaphase to anaphase. Cyclin A47 associa...