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.