RB1

Fig1. Beyond binding and inhibiting E2F, Rb1 was implicated in the regulation of several signaling pathways. (Radoslav Janostiak, 2022)

What is RB1 protein?

RB1 (RB transcriptional corepressor 1) gene is a protein coding gene which situated on the long arm of chromosome 13 at locus 13q14. The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. The RB1 protein is consisted of 928 amino acids and its molecular mass is approximately 106.2 kDa.

What is the function of RB1 protein?

RB1 protein is a key tumor suppressor protein that plays an important role in cell cycle regulation, cell differentiation and apoptosis. RB1 inhibits transcription activity mainly by binding to members of the transcription factor E2F family, thereby preventing cells from entering the S phase and inhibiting cell proliferation. In addition, RB1 can further regulate gene expression by interacting with other proteins to influence chromatin remodeling and histone modification.

RB1 Related Signaling Pathway

By binding to members of the E2F transcription factor family, RB1 inhibits its activity, thereby preventing cells from entering the S phase and inhibiting cell proliferation. RB1 can interact with p53 protein to enhance the transcriptional activity of p53, thereby promoting DNA damage repair or inducing apoptosis. RB1 can interact with chromatin remodeling complexes and histone modifying enzymes to influence gene expression. RB1 is involved in regulating the process of cell differentiation by interacting with specific transcription factors to inhibit or activate the expression of specific genes.

RB1 Related Diseases

RB1 protein is a tumor suppressor protein whose loss of function or inactivation is strongly associated with the development of many types of cancer, including retinoblastoma, breast cancer, colorectal cancer, osteosarcoma, and lymphoma. In addition, RB1 gene mutation is also an important genetic factor in familial breast cancer and colorectal cancer. The loss of RB1 protein's important role in cell cycle regulation, cell differentiation, and apoptosis can lead to uncontrolled cell proliferation, which can lead to cancer.

Fig2. Inactivation of RB during cancer progression results in multiple malignant phenotypes. (Shunsuke Kitajima, 2017)

Bioapplications of RB1

RB1 protein has important application value in clinical research. Due to its important role in cell cycle regulation and tumorigenesis and development, RB1 has become a potential therapeutic target for a variety of tumors. For example, inhibitors targeting RB1 are being developed to treat tumors with RB1 deletion or mutation, such as breast cancer and non-small cell lung cancer. In addition, the expression level of RB1 protein is also used as a prognostic indicator for certain types of cancer. By studying the expression and function of RB1, scientists hope to better understand how cancer occurs and develop more effective treatments.

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.

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.

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