Abstract
BackgroundThe RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. However, there are two kinds of E2Fs (repressive E2Fs and active E2Fs) and three RB family members in human. Till now, the detail evolutionary history of these protein families and how RB-E2F pathway evolved in different organisms remain poorly explored.ResultsWe performed a comprehensive evolutionary analysis of E2F, RB and DP (dimerization partners of E2Fs) protein family in representative eukaryotic organisms. Several interesting facts were revealed. First, orthologues of RB, E2F, and DP family are present in several representative unicellular organisms and all multicellular organisms we checked. Second, ancestral E2F, RB genes duplicated before placozoans and bilaterians diverged, thus E2F family was divided into E2F4/5 subgroup (including repressive E2Fs: E2F4 and E2F5) and E2F1/2/3 subgroup (including active E2Fs: E2F1, E2F2 and E2F3), RB family was divided into RB1 subgroup (including RB1) and RBL subgroup (including RBL1 and RBL2). Third, E2F4 and E2F5 share more sequence similarity with the predicted E2F ancestral sequence than E2F1, E2F2 and E2F3; E2F4 and E2F5 also possess lower evolutionary rates and higher purification selection pressures than E2F1, E2F2 and E2F3. Fourth, for RB family, the RBL subgroup proteins possess lower evolutionary rates and higher purification selection pressures compared with RB subgroup proteins in vertebrates,ConclusionsProtein evolutionary rates and purification selection pressures are usually linked with protein functions. We speculated that function conducted by E2F4/5 subgroup and RBL subgroup proteins might mainly represent the ancient function of RB-E2F pathway, and the E2F1/2/3 subgroup proteins and RB1 protein might contribute more to functional diversification in RB-E2F pathway. Our results will enhance the current understanding of RB-E2F pathway and will also be useful to further functional studies in human and other model organisms.ReviewersThis article was reviewed by Dr. Pierre Pontarotti, Dr. Arcady Mushegian and Dr. Zhenguo Lin (nominated by Dr. Neil Smalheiser).
Highlights
The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants
The origination and distribution of E2F1-6, E2F7-8, RB, and DP family proteins in Eukaryotes Based on protein similarity searching and domain associations checking (Detail in material and methods section), E2F1-6, E2F7/8, RB, DP family proteins were identified in representative organisms
We found that unicellular organisms, D. discoideum AX4, Oryza sativa (Os). tauri, and M. brevicollis contain the representative orthologues of E2F1-6, DP, and RB family
Summary
The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. There are two kinds of E2Fs (repressive E2Fs and active E2Fs) and three RB family members in human. Proteins that are related to the retinoblastoma tumor suppressor RB and the E2F transcription factor are conserved in most eukaryotic lineages, including animals and plants [2]. RB-family members are generally believed to function through their effects on the transcription of genes regulated by the. E2F proteins, which share a conserved DNA binding domain, can bind to overlapping sets of target promoters. E2F1-6 all possess one E2F-TDP domain, and E2F1, E2F2, and E2F3 are generally considered as the ‘active E2Fs’ on the basis of their ability to potently activate transcription. E2F6, possessing one E2F-TDP domain but no RB binding domain, can not bind to RB family proteins [5]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have