Submit Manuscript  

Article Details


A Possible Modulation Mechanism of Intramolecular and Intermolecular Interactions for NCAM Polysialylation and Cell Migration

[ Vol. 19 , Issue. 25 ]

Author(s):

Bo Lu, Xue-Hui Liu, Si-Ming Liao, Zhi-Long Lu, Dong Chen, Frederic A. Troy II, Ri-Bo Huang* and Guo-Ping Zhou*   Pages 2271 - 2282 ( 12 )

Abstract:


Polysialic acid (polySia) is a novel glycan that posttranslationally modifies neural cell adhesion molecules (NCAMs) in mammalian cells. Up-regulation of polySia-NCAM expression or NCAM polysialylation is associated with tumor cell migration and progression in many metastatic cancers and neurocognition. It has been known that two highly homologous mammalian polysialyltransferases (polySTs), ST8Sia II (STX) and ST8Sia IV (PST), can catalyze polysialylation of NCAM, and two polybasic domains, polybasic region (PBR) and polysialyltransferase domain (PSTD) in polySTs play key roles in affecting polyST activity or NCAM polysialylation. However, the molecular mechanisms of NCAM polysialylation and cell migration are still not entirely clear. In this minireview, the recent research results about the intermolecular interactions between the PBR and NCAM, the PSTD and cytidine monophosphate-sialic acid (CMP-Sia), the PSTD and polySia, and as well as the intramolecular interaction between the PBR and the PSTD within the polyST, are summarized. Based on these cooperative interactions, we have built a novel model of NCAM polysialylation and cell migration mechanisms, which may be helpful to design and develop new polysialyltransferase inhibitors.

Keywords:

NMR, Sialic acid (Sia), Polysialic acid (polySia), Polysialyltransferases, ST8Sia II (STX), ST8Sia IV (PST), Neural cell adhesion molecules (NCAMs), PSTD, PBR, Cancer metastasis, Phyre2 server.

Affiliation:

The National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, Nanning, Guangxi 530007, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, The National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, Nanning, Guangxi 530007, The National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, Nanning, Guangxi 530007, The National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, Nanning, Guangxi 530007, Department of Biochemistry and Molecular Medicine, University of California School of Medicine, Davis, CA, 95817, The National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, Nanning, Guangxi 530007, The National Engineering Research Center for Non-Food Biorefinery, Guangxi Academy of Sciences, Nanning, Guangxi 530007

Graphical Abstract:



Read Full-Text article