A Fresh Look at the Structure, Regulation, and Functions of Fodrin.

Fodrin and its erythroid cell-specific isoform spectrin are actin-associated fibrous proteins that play crucial roles in the maintenance of structural integrity in mammalian cells, which is necessary for proper cell function. Normal cell morphology is altered in diseases such as various cancers and certain neuronal disorders. Fodrin and spectrin are two-chain (αβ) molecules that are encoded by paralogous genes and share many features but also demonstrate certain differences.

α-Fodrin is required for the organization of functional microtubules during mitosis.

The cytoskeleton protein α-fodrin plays a major role in maintaining structural stability of membranes. It was also identified as part of the brain γ-tubulin ring complex, the major microtubule nucleator. Here, we investigated the requirement of α-fodrin for microtubule spindle assembly during mitotic progression.

Binding of alpha-fodrin to gamma-tubulin accounts for its role in the inhibition of microtubule nucleation.

Non-erythroid spectrin or fodrin is present as part of the γ-tubulin ring complex (γ-TuRC) in brain tissue and brain derived cells. Here, we show that fodrin, which is otherwise known for providing structural support to the cell membrane, interacts directly with γ-tubulin within the γ-TuRC through a GRIP2-like motif. Turbidometric analysis of microtubule polymerization with nucleation-potent γ-TuRC isolated from HEK-293 cells that lack fodrin and the γ-TuRC from goat brain that contains fodrin shows inefficiency of the latter to promote nucleation.

Cell cycle-dependent regulation of cytoglobin by Skp2.

Cytoglobin (Cygb) is a cellular haemoprotein belonging to the globin family with ambiguous biological functions. Downregulation of Cygb in many cancers is indicative of its tumour-suppressive role. This is the first report showing the cell cycle regulation of Cygb, which was found to peak at G1 and rapidly decline in S phase.

Oncogenic Human Papillomavirus 16E7 modulates SUMOylation of FoxM1b.

The oncogenic transcription factor Forkhead box M1b (FoxM1b), a key regulator of cell cycle, is often overexpressed in many human cancers. Interestingly, posttranslational modifications are known to play important role in regulating the levels and activity of FoxM1b. The purpose of the present study was to characterize the SUMOylation of FoxM1b and identify the functional consequences including viral pathogenesis.

DNA damage induced activation of Cygb stabilizes p53 and mediates G1 arrest.

Cytoglobin (Cygb) is an emerging tumor suppressor gene silenced by promoter hypermethylation in many human tumors. So far, the precise molecular mechanism underlying its tumor suppressive function remains poorly understood. Here, we identified Cygb as a genotoxic stress-responsive hemoprotein upregulated upon sensing cellular DNA damage.

Cytoglobin in tumor hypoxia: novel insights into cancer suppression.

Emerging new and intriguing roles of cytoglobin (Cygb) have attracted considerable attention of cancer researchers in recent years. Hypoxic upregulation of Cygb as well as its altered expression in various human cancers suggest another possible role of this newly discovered globin in tumor cell response under low oxygen tension. Since tumor hypoxia is strongly associated with malignant progression of disease and poor treatment response, it constitutes an area of paramount importance for rational design of cancer selective therapies.

High-risk HPV16E6 stimulates hADA3 degradation by enhancing its SUMOylation.

Despite significant research, our understanding of the molecular mechanisms of Human Papilloma Virus (HPV) induced cancers remains incomplete. Majority of invasive cervical cancers are caused by high-risk HPV 16 and 18. Two potent HPV oncoproteins, E6 and E7, promote human malignancies by disrupting the activities of key regulators of cell proliferation and apoptosis.