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Conjugation of polymer to protein has been widely employed in therapeutics, medicine, biotechnology, and enzymatic catalysis. The synergistic effect benefits both counterparts and potentially overcomes their inherent limitations. This article reviews the strategies for the site-specific synthesis of well-defined protein-polymer conjugates, aiming to provide a toolbox for the community. First, it is essential to set a definite reactive site on the protein because the position of the reaction site can directly influence the reaction activity and the bioactivity of the protein after modification. The origins of the specific functional groups on protein include the utilization of the unique natural amino acid, mutagenesis to introduce a sole reactive amino acid, chemical modification, noncanonical amino acid incorporation, and enzyme-mediated introduction of functional groups. Second, the main conjugation methods, i.e., "grafting to" and "grafting from" methods, are summarized and compared with each other. In the "grafting to" method, a comprehensive investigation on the reactions used to attach an end functional polymer chain to a protein is conducted according to the position of the target site and its nature. In the "grafting from" method, a comparison between the commonly used controlled polymerization, i.e., atom transfer radical polymerization (ATRP) and reversible addition-fragmentation transfer (RAFT), is surveyed. Further, a special case where a noncovalent bond is adopted to link the protein and polymer together is investigated due to its high specificity and reversibility, typically biotin-(strept)avidin-based interactions and metal-mediated conjugation. Finally, applications of protein-polymer conjugates in drug delivery, biomedicine, biosensor, and the disease-related protein self-assembly are illustrated. This precise review on the conjugation of polymer chain to protein to form well-defined protein-polymer conjugates summarizes the representative strategies and may provide useful cues in the areas of biotechnology, therapeutic drugs, and biomedicine.

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BackgroundCervical cancer (CC) is one of the most common cancers among females worldwide. Spindle and kinetochore-associated complex subunit 3 (SKA3), located on chromosome 13q, was identified as a novel gene involved in promoting malignant transformation in cancers. However, the function and underlying mechanisms of SKA3 in CC remain unknown. Using the Oncomine database, we found that expression of SKA3 mRNA is higher in CC tissues than in normal tissues and is linked with poor prognosis.MethodsIn our study, immunohistochemistry showed increased expression of SKA3 in CC tissues. The effect of SKA3 on cell proliferation and migration was evaluated by CCK8, clone formation, Transwell and wound-healing assays in HeLa and SiHa cells with stable SKA3 overexpression and knockdown. In addition, we established a xenograft tumor model in vivo.ResultsSKA3 overexpression promoted cell proliferation and migration and accelerated tumor growth. We further identified that SKA3 is involved in regulating cell cycle progression and the PI3K/Akt signaling pathway via RNA-sequencing (RNA-Seq) and gene set enrichment analyses. Western blotting results revealed that SKA3 overexpression increased levels of p-Akt, cyclin E2, CDK2, cyclin D1, CDK4, E2F1 and p-Rb in HeLa cells. Additionally, the use of an Akt inhibitor (GSK690693) significantly reversed the cell proliferation capacity induced by SKA3 overexpression in HeLa cells.ConclusionsWe suggest that SKA3 overexpression contributes to CC cell growth and migration by promoting cell cycle progression and activating the PI3K–Akt signaling pathway, which may provide potential novel therapeutic targets for CC treatment.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0670-4) contains supplementary material, which is available to authorized users.