Brief. Bioinformatics - Apoptosis regulatory protein-protein interaction demonstrates hierarchical scale-free fractal network.

Tópicos

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Resumo

Dysregulation or inhibition of apoptosis favors cancer and many other diseases. Understanding of the network interaction of the genes involved in apoptotic pathway, therefore, is essential, to look for targets of therapeutic intervention. Here we used the network theory methods, using experimentally validated 25 apoptosis regulatory proteins and identified important genes for apoptosis regulation, which demonstrated a hierarchical scale-free fractal protein-protein interaction network. TP53, BRCA1, UBIQ and CASP3 were recognized as a four key regulators. BRCA1 and UBIQ were also individually found to control highly clustered modules and play an important role in the stability of the overall network. The connection among the BRCA1, UBIQ and TP53 proteins was found to be important for regulation, which controlled their own respective communities and the overall network topology. The feedback loop regulation motif was identified among NPM1, BRCA1 and TP53, and these crucial motif topologies were also reflected in high frequency. The propagation of the perturbed signal from hubs was found to be active upto some distance, after which propagation started decreasing and TP53 was the most efficient signal propagator. From the functional enrichment analysis, most of the apoptosis regulatory genes associated with cardiovascular diseases and highly expressed in brain tissues were identified. Apart from TP53, BRCA1 was observed to regulate apoptosis by influencing motif, propagation of signals and module regulation, reflecting their biological significance. In future, biochemical investigation of the observed hub-interacting partners could provide further understanding about their role in the pathophysiology of cancer.

Resumo Limpo

dysregul inhibit apoptosi favor cancer mani diseas understand network interact gene involv apoptot pathway therefor essenti look target therapeut intervent use network theori method use experiment valid apoptosi regulatori protein identifi import gene apoptosi regul demonstr hierarch scalefre fractal proteinprotein interact network tp brca ubiq casp recogn four key regul brca ubiq also individu found control high cluster modul play import role stabil overal network connect among brca ubiq tp protein found import regul control respect communiti overal network topolog feedback loop regul motif identifi among npm brca tp crucial motif topolog also reflect high frequenc propag perturb signal hub found activ upto distanc propag start decreas tp effici signal propag function enrich analysi apoptosi regulatori gene associ cardiovascular diseas high express brain tissu identifi apart tp brca observ regul apoptosi influenc motif propag signal modul regul reflect biolog signific futur biochem investig observ hubinteract partner provid understand role pathophysiolog cancer

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