The first step in bacterial cytokinesis is the assembly of a stable but dynamic cytokinetic ring made up of the essential tubulin homolog FtsZ at the future site of division. Although FtsZ and its role in cytokinesis have been studied extensively, the precise architecture of the in vivo medial FtsZ ring (Z ring) is not well understood. Recent advances in superresolution imaging suggest that the Z ring comprises short, discontinuous, and loosely bundled FtsZ polymers, some of which are tethered to the membrane. A diverse array of regulatory proteins modulate the assembly, stability, and disassembly of the Z ring via direct interactions with FtsZ. Negative regulators of FtsZ play a critical role in ensuring the accurate positioning of FtsZ at the future site of division and in maintaining Z ring dynamics by controlling FtsZ polymer assembly/disassembly processes. Positive regulators of FtsZ are essential for tethering FtsZ polymers to the membrane and promoting the formation of stabilizing lateral interactions, permitting assembly of a mature Z ring. The past decade has seen the identification of several factors that promote FtsZ assembly, presumably through a variety of distinct molecular mechanisms. While a few of these proteins are broadly conserved, many positive regulators of FtsZ assembly are limited to small groups of closely related organisms, suggesting that FtsZ assembly is differentially modulated across bacterial species. In this review, we focus on the roles of positive regulators in Z ring assembly and in maintaining the integrity of the cytokinetic ring during the early stages of division. Bacterial cytokinesis is mediated by a macromolecular protein machine that is accurately positioned in space and time during the cell cycle. The earliest defined event during cytokinesis is the assembly of a polymeric FtsZ structure at the site of future division known as the FtsZ ring, or Z ring (1). The Z ring serves as a scaffold for the recruitment of other division proteins (2-5). FtsZ, a tubulin homolog, forms homopolymeric linear protofilaments upon binding GTP, and these filaments subsequently disassemble upon hydrolysis of the bound nucleotide (6-9). Approximately 30% of cellular FtsZ is present in the ring, and fluorescence recovery after photobleaching (FRAP) studies reveal that there is dynamic exchange between FtsZ molecules in the ring polymers and FtsZ monomers or short oligomers in the cytoplasm (10, 11).In Escherichia coli and Bacillus subtilis, cytokinesis can be separated chronologically into the following three steps: (i) assembly and stabilization of the Z ring at the future division site and, following a lag, (ii) recruitment of downstream division proteins, many of which are essential to form a constriction-competent division complex, and lastly, (iii) constriction of the Z ring coordinated with synthesis and splitting of septal peptidoglycan, leading to invagination of the cell membrane and division into two daughter cells (Fig. 1A) (2, 12, 13). The force required for constriction is likely...

Background: As an epigenetic regulator, the transcriptional intermediary factor 1β (TIF1β)/ KAP1/TRIM28) has been linked to gene expression and chromatin remodeling at specific loci by association with members of the heterochromatin protein 1 (HP1) family and various other chromatin factors. The interaction between TIF1β and HP1 is crucial for heterochromatin formation and maintenance. The HP1-box, PXVXL, of TIF1β is responsible for its interaction with HP1. However, the underlying mechanism of how the interaction is regulated remains poorly understood.

Triple-negative breast cancer (TNBC) is an aggressive cancer subtype for which effective therapies are lacking. Epidermal growth factor receptor (EGFR) is overexpressed in various types of TNBC cells, and several EGFR-specific immunotherapies have been used to treat cancer patients. Chimeric antigen receptor engineered T (CAR-T) cells have also been used as cancer therapies. In this study, we generated two types of EGFR-specific CAR-modified T cells using lentiviral vectors with DNA sequences encoding the scFv regions of two anti-EGFR antibodies. The cytotoxic and antitumor effects of these CAR-modified T cells were examined in cytokine release and cytotoxicity assays in vitro and in tumor growth assays in TNBC cell line- and patient-derived xenograft mouse models. Both types of EGFR-specific CAR-T cells were activated by high-EGFR-expressing TNBC cells and specifically triggered TNBC cell lysis in vitro. Additionally, the CAR-T cells inhibited growth of cell-line- and patient-derived xenograft TNBC tumors in mice. These results suggest that EGFR-specific CAR-T cells might be a promising therapeutic strategy in patients with high-EGFR-expressing TNBC.