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Ben-Hur, V., Denichenko, P., Siegfried, Z., Maimon, A., Krainer, A., Davidson, B., et al. (2013) S6K1 alternative splicing modulates its oncogenic activity and regulates mTORC1. Cell Reports, 3, 103-115. doi:10.1016/j.celrep.2012.11.020

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• TITLE: Operative sequentiality in tumor differentiation and progression as protein molecular structure and sequence context in modulating alternative splicing events

  AUTHORS: Lawrence M. Agius

  KEYWORDS: RNA Splicing; Neoplasms; Tumorigenesis; Protein Isoforms

  JOURNAL NAME: Open Journal of Genetics, Vol.3 No.2, June 25, 2013

  ABSTRACT: This review article discusses dimensional reconstruction of alternative splicing that not only affects primarily the distributional dimensions of isoforms of various protein species but especially influences the nature of interactivity events between various protein species and also the structure of the given protein molecules. In such terms, disorders of differentiation of individual tumors and of tumor types and subtypes would correlate with distinctive dimensions of expression of a limited number of genes in various modes of expressed selectivity programs. In particular, the differentiation programs of normal tissues would correlate with combinatorial systems of splicing factors and of auxiliary factors in the development of patterns of gene expression. The significance of mis-splicing events is consonant with the wide range of phenotypic expression of neoplastic lesions and in the great variety of differentiation patterns and also of the variable degrees of differentiation of various components of a given neoplasm. The structure of given protein isoforms resulting from alternative splicing correlate with the sequence context of exons in the enhancement or inhibition of splicing events and would also influence pathobiologic behavior patterns of given neoplastic lesions. The development of abnormal cell signalling pathways and of interactivity patterns in a combinatorial way would directly influence the stability and trafficking dynamics of given protein molecular species in inducing an abundance of protein isoform production. Series of multi-component systems ranging from receptivity to consequential pathways of development of differential phenotype would allow for a high degree of modulatory effect within systems implicating in particular the interactions of individual tumor cells with each other and with the matrix components. It is within the context of constitutive versus alternative splicing events that this review article proposes that proportional recreation of differentiation pathways promotes a self-progression of the pathobiologic processes of a given neoplastic lesion.