Beyond What Your Retina Can See: Similarities of Retinoblastoma Function between Plants and Animals, from Developmental Processes to Epigenetic Regulation

Abstract

The Retinoblastoma protein (pRb) is a key cell cycle regulator conserved in a wide variety of organisms. Experimental analysis of pRb’s functions in animals and plants has revealed that this protein participates in cell proliferation and differentiation processes. In addition, pRb in animals and its orthologs in plants (RBR), are part of highly conserved protein complexes which suggest the possibility that analogies exist not only between functions carried out by pRb orthologs themselves, but also in the structure and roles of the protein networks where these proteins are involved. Here, we present examples of pRb/RBR participation in cell cycle control, cell differentiation, and in the regulation of epigenetic changes and chromatin remodeling machinery, highlighting the similarities that exist between the composition of such networks in plants and animals.

Direct Regulation of DNA Repair by E2F and RB in Mammals and Plants: Core Function or Convergent Evolution?

“…The LECA cell cycle network also likely included at least one CDK and multiple cyclins that regulated events in different phases of the cell cycle ( Figure 1 B). Studies from a variety of eukaryotes have demonstrated how RB and E2F homologs link the activity of CDKs with the periodic expression of genes important for cell cycle progression and cell division [ 13 , 17 , 27 ]. Phosphorylation of RB by D-type cyclin-CDKs initially allows the induction of genes important for the G1/S phase transition, including G1/S phase cyclins, like human CCNE (cyclin E) and CCNA (cyclin A).…”

“…RB homologs in animals and plants actively repress transcription by interacting with and recruiting chromatin modifying enzymes to the promoters of E2F target genes [ 13 , 17 , 27 , 35 , 36 ]. Several of these chromatin modifying enzymes contain a LxCxE amino acid motif that binds to a conserved cleft in the RB pocket domain and allows RB to bind both the chromatin modifiers and E2F factors simultaneously [ 37 ].…”

“…Moreover, the HPV E7 protein, and many other proteins from viruses that infect both animals and plants, also contain LxCxE motifs that are used to disrupt RB-E2F complexes [ 5 , 8 , 38 ]. Apparently, a number of unrelated DNA viruses have independently evolved LxCxE motif-containing proteins to target RB-E2F complexes as a common strategy for virus replication in both animals and plants [ 17 , 39 ].…”

“…This includes roles for RB and E2F in the first step of differentiation: The asymmetric division of stem cells. This asymmetric division gives rise to one daughter cell that maintains “stemness” in a quiescent state and another daughter that proliferates and differentiates into a tissue [ 13 , 17 , 48 , 51 , 52 , 53 , 54 , 55 ]. Genetic experiments in animals and plants have provided numerous examples showing how RB and E2F family members regulate both tissue differentiation and organismal development [ 56 , 57 ].…”

“…RB family members are identified by a conserved pocket domain, which binds to E2F proteins. E2F family members are identified by their DNA binding domains, which recognize similar DNA consensus binding sites in the promoters of cell cycle-regulated genes [ 13 , 15 , 16 , 17 ]. These E2F target genes encode proteins important for DNA replication and mitosis and are actively repressed when RB is bound to E2F.…”