RB1

Case Study 1: Vaibhav Chand, 2022

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. The retinoblastoma protein (RB1), a regulator of cell proliferation, is functionally inactivated in HCC by CYCLIN D/E-mediated phosphorylation. However, the mechanism of RB1-inactivation is unclear because only small percentages of HCCs exhibit amplification of CYCLIN D/E or mutations in the CDK-inhibitory genes. The researchers show that FOXM1, which is overexpressed and critical for HCC, plays essential roles in inactivating RB1 and suppressing RB1-induced senescence of the HCC cells. Mechanistically, FOXM1 binds RB1 and DNMT3B to repress the expression of FOXO1, leading to a decrease in the levels of the CDK-inhibitors, creating an environment for phosphorylation and inactivation of RB1. Consistent with that, inhibition of FOXM1 causes increased expression of FOXO1 with consequent activation of RB1, leading to senescence of the HCC cells, in vitro and in vivo. Also, repression-deficient mutants of FOXM1 induce senescence that is blocked by depletion of RB1 or FOXO1.

Fig1. The interactions between RB1, DNMT3B and FOXM1 were assayed by western blotting.

Fig2. The repression mechanism of FOXM1 regulates stemness and invasiveness by counteracting RB1-induced cellular senescence.

Case Study 2: Ankur Sharma, 2007

The retinoblastoma tumor suppressor protein (RB), a critical mediator of cell cycle progression, is functionally inactivated in the majority of human cancers, including prostatic adenocarcinoma. The importance of RB tumor suppressor function in this disease is evident because 25% to 50% of prostatic adenocarcinomas harbor aberrations in RB pathway. However, no previous studies challenged the consequence of RB inactivation on tumor cell proliferation or therapeutic response. Here, the researchers show that RB depletion facilitates deregulation of specific E2F target genes, but does not confer a significant proliferative advantage in the presence of androgen. These data indicate that RB deficiency can facilitate bypass of first-line hormonal therapies used to treat prostate cancer. Given the established effect of RB on DNA damage checkpoints, these studies were then extended to determine the impact of RB depletion on the response to cytotoxic agents used to treat advanced disease.

Fig3. Stable clones of RB knockdown (shRB1) or control (shCon1) were generated and tested for RB expression levels using immunofluorescence.

Fig4. RB depletion reduces the efficacy of single agent–based hormonal intervention.

Fig1. αvβ3 signaling pathway in prostate cancer cells. (Deborah L Burkhart, 2019)

Fig2. Various oncogenic signals contribute to metabolic perturbation in cancer cells. (Chiaki Takahashi, 2012)

RB1 involved in several pathways and played different roles in them. We selected most pathways RB1 participated on our site, such as Cell cycle, Hepatitis B, HTLV-I infection, which may be useful for your reference. Also, other proteins which involved in the same pathway with RB1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

RB1 has several biochemical functions, for example, DNA binding, RNA polymerase II activating transcription factor binding, androgen receptor binding. Some of the functions are cooperated with other proteins, some of the functions could acted by RB1 itself. We selected most functions RB1 had, and list some proteins which have the same functions with RB1. You can find most of the proteins on our site.

RB1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with RB1 here. Most of them are supplied by our site. Hope this information will be useful for your research of RB1.

E7