Roles of plant retinoblastoma protein: cell cycle and beyond

Abstract

The human retinoblastoma (RB1) protein is a tumor suppressor that negatively regulates cell cycle progression through its interaction with members of the E2F/DP family of transcription factors. However, RB-related (RBR) proteins are an early acquisition during eukaryote evolution present in plant lineages, including unicellular algae, ancient plants (ferns, lycophytes, liverworts, mosses), gymnosperms, and angiosperms. The main RBR protein domains and interactions with E2Fs are conserved in all eukaryotes and not only regulate the G1/S transition but also the G2/M transition, as part of DREAM complexes. RBR proteins are also important for asymmetric cell division, stem cell maintenance, and the DNA damage response (DDR). RBR proteins play crucial roles at every developmental phase transition, in association with chromatin factors, as well as during the reproductive phase during female and male gametes production and embryo development. Here, we review the processes where plant RBR proteins play a role and discuss possible avenues of research to obtain a full picture of the multifunctional roles of RBR for plant life.

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 ].…”

“…For example, complete or conditional inactivation of Rb1 in mice impacts hematopoiesis, neurogenesis, adipogenesis, myogenesis, and osteogenesis [ 58 , 59 , 60 , 61 , 62 , 63 , 64 ]. Genetic manipulation of RB and E2F homologs in Arabidopsis has also demonstrated important roles for these proteins in differentiation and the development of plant tissues, including the vascular system, roots, leaves, flowers, and seeds [ 17 , 27 , 36 ].…”

“…For example, RB regulates erythropoiesis in mice by interacting with the GATA1 transcription factor, which contains an LxCxE motif conserved in other animal GATA1 homologs [ 67 ]. A number of tissue-specific transcription factors in Arabidopsis also contain LxCxE motifs and cooperate with the sole RB homolog, RBR, to regulate asymmetric division and the development of several distinct plant tissues [ 17 , 27 , 68 ].…”

Correlation between Family RB1 Gene Pathogenic Variant with Clinical Features and Prognosis of Retinoblastoma under 5 Years Old

“…The occurrence and development of RB are closely related to the pathogenic variant of the tumor suppressor RB1 gene [7]. Since the 1980s, the RB1 gene on the long arm of chromosome 13 (13q14) has been recognized as the RB tumor suppressor gene for the first time, and its pathogenic variant is involved in the occurrence of RB [5,6,[8][9][10]. Compelling studies [1,5,6,[11][12][13][14][15] indicated that the RB1 gene is an allele encoding retinoblastoma protein (pRB), and the lack of monitoring or inactivation of RB1 will lead to a decline in cell proliferation regulation function thus resulting in abnormal cell proliferation.…”