Abstract Several FDA-approved adjuvant formulations, such as saponins and lipid nanoparticles, have been shown to mediate their effects in part through the NLRP3 inflammasome. These formulations are among most potent adjuvants use, but they limited by poor synthetic control immunotoxic side effects. New small molecule targeting inflammasome would allow broader implementation of subunit- nucleot...

The precise cell-cycle alternation of S phase and mitosis is controlled by alternating competence of nuclei to respond to S-phase-inducing factors [1]. Nuclei acquire competence to replicate at the low point in cyclin-dependent kinase (Cdk) activities that follows mitotic destruction of cyclins. The elevation of Cdk activity late in G1 is thought to drive cells into S phase and to block replica...

Using the conditionally immortalized human cell line tsFHI, we have investigated the role of cyclin-dependent kinase inhibitors (CKIs) in intestinal epithelial cell differentiation. Expression of cyclins, cyclin-dependent kinases (Cdk), and CKIs was examined under conditions promoting growth, growth arrest, or expression of differentiated traits. Formation of complexes among cell cycle regulato...

The response of cells to extracellular mitogenic signals and commitment to enter G1 phase, are regulated by the D-type cyclins (D1, D2 and D3). Once induced they heterodimerize with and activate either cyclin dependent kinase 4 or 6 (CDK4 or CDK6). Cyclin D-CDK4 and D-CDK6 kinases phosphorylate and inactivate the retinoblastoma family of proteins, leading to release and derepression of E2F tran...

Progestin antagonists inhibit the proliferation of progesterone receptor-positive cells, including breast cancer cells, by G1 phase-specific actions, but the molecular targets involved are not defined. Reduced phosphorylation of pRB, a substrate for G1 cyclin-dependent kinases (CDKs) in vivo, was apparent after 9 h treatment of T-47D breast cancer cells with the antiprogestins RU 486 or ORG 317...

After sister chromatid splitting at anaphase onset, exit from mitosis comprises an ordered series of events. Dephosphorylation of numerous mitotic substrates, which were phosphorylated by cyclin-dependent kinase (Cdk), is thought to bring about mitotic exit, but how temporal ordering of mitotic exit events is achieved is poorly understood. Here, we show, using budding yeast, that dephosphorylat...

In the present study, we report the cyclin-dependent kinase (Cdk)inhibitory activity of a series of p21 (p21) peptide fragments spanning the whole protein against the cyclin D1/Cdk4 and cyclin E/Cdk2 enzymes. The most potent p21 peptide tested in our initial peptide series, designated W10, spanned amino acids 139 to 164, a region of p21 that has been found independently to bind to proliferating...

Genomic alterations leading to aberrant activation of cyclin/ cyclin-dependent kinase (cdk) complexes drive the pathogenesis of many common human tumor types. In the case of glioblastoma multiforme (GBM), these alterations are most commonly due to homozygous deletion of p16 and less commonly due to genomic amplifications of individual genes encoding cyclins or cdks. Here, we describe deletion o...

Using immunodepletion of cyclin E and the inhibitor protein p21WAF/CIP1, we demonstrate that the cyclin E protein, in association with Cdk2, is required for the elongation phase of replication on single-stranded substrates. Although cyclin E/Cdk2 is likely to be the major target by which p21 inhibits the initiation of sperm DNA replication, p21 can inhibit single-stranded replication through a ...