The Retinoblastoma Protein Binds to a Family of E2F Transcription Factors

Abstract

E2F is a transcription factor that helps regulate the expression of a number of genes that are important in cell proliferation. Recently, several laboratories have isolated a cDNA clone that encodes an E2F-like protein, known as E2F-1. Subsequent characterization of this protein showed that it had the properties of E2F, but it was difficult to account for all of the suggested E2F activities through the function of this one protein. Using low-stringency hybridization, we have isolated cDNA clones that encode two additional E2F-like proteins, called E2F-2 and E2F-3. The chromosomal locations of the genes for E2F-2 and E2F-3 were mapped to 1p36 and 6q22, respectfully, confirming their independence from E2F-1. However, the E2F-2 and E2F-3 proteins are closely related to E2F-1. Both E2F-2 and E2F-3 bound to wild-type but not mutant E2F recognition sites, and they bound specifically to the retinoblastoma protein in vivo. Finally, E2F-2 and E2F-3 were able to activate transcription of E2F-responsive genes in a manner that was dependent upon the presence of at least one functional E2F binding site. These observations suggest that the E2F activities described previously result from the combined action of a family of proteins.

Understanding Retinoblastoma Post-Translational Regulation for the Design of Targeted Cancer Therapies

“…E2F2, E2F3, E2F4 and E2F5 members contain Rb1-binding domains similar to E2F1 and interact with Rb1 [48,49]. The interaction of Rb1 with E2F2 and E2F3 results in blockage of their pro-proliferative function, which is consistent with their established role as transcriptional activators [48,50]. However, E2F4 and E2F5 are considered transcriptional repressors and therefore the function of their interaction with Rb1 is different.…”

p53-mediated neurodegeneration in the absence of the nuclear protein Akirin2

“…Of particular interest to this study, the retinoblastoma tumor suppressor protein (pRb) suppresses the G1/S phase transition. In quiescent neurons, hypophosphorylated pRb represses members of the E2F protein family to block cell cycle progression ( Lees et al., 1993 ). In response to a mitogenic stimulant, D-type cyclins are synthesized and bind to Cdk4 or Cdk6.…”

Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment

“…63 , 64 Alterations in Na + -K + -ATPase activity also represent an important mechanism of diabetics-induced neurotoxicity. 65 In the same vein, nitric oxide, as a neurotransmitter, is reported to mediate synaptic activity, neural plasticity, and memory function. 66 Interestingly, we found that treatment with AESTL reverses the overexpression of Na + -K + -ATPase, COX-2 and NO to the baseline value, hence suggesting the anti-inflammatory and therapeutic role of AESTL in the maintenance of ion gradients across biological membranes and thus confer significant protection to the brain by stabilizing the functional integrity of the membrane.…”