Retinoblastoma-Binding Protein 2
Retinoblastoma Binding Proteins
Retinoblastoma
Retinoblastoma Protein
Genes, Retinoblastoma
BRCA1 interacts with components of the histone deacetylase complex. (1/70)
Germ-line mutations in the BRCA1 tumor-suppressor gene are associated with an increased susceptibility to breast and ovarian cancer. BRCA1 contains a carboxyl-terminal domain (BRCT) that is shared with several other proteins involved in maintaining genome integrity. In an effort to understand the function of BRCA1, we sought to isolate proteins that interact with the BRCT domain. Purified BRCT polypeptide was used as a probe to screen a human placenta cDNA expression library by Far Western analysis. Here we report that BRCA1 interacts in vivo and in vitro with the Rb-binding proteins, RbAp46 and RbAp48, as well as with Rb. Moreover, the BRCT domain associates with the histone deacetylases HDAC1 and HDAC2. These results demonstrate that BRCA1 interacts with components of the histone deacetylase complex, and therefore may explain the involvement of BRCA1 in multiple processes such as transcription, DNA repair, and recombination. (+info)Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. (2/70)
ATP-dependent nucleosome remodeling and core histone acetylation and deacetylation represent mechanisms to alter nucleosome structure. NuRD is a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. The histone deacetylases HDAC1 and HDAC2 and the histone binding proteins RbAp48 and RbAp46 form a core complex shared between NuRD and Sin3-histone deacetylase complexes. The histone deacetylase activity of the core complex is severely compromised. A novel polypeptide highly related to the metastasis-associated protein 1, MTA2, and the methyl-CpG-binding domain-containing protein, MBD3, were found to be subunits of the NuRD complex. MTA2 modulates the enzymatic activity of the histone deacetylase core complex. MBD3 mediates the association of MTA2 with the core histone deacetylase complex. MBD3 does not directly bind methylated DNA but is highly related to MBD2, a polypeptide that binds to methylated DNA and has been reported to possess demethylase activity. MBD2 interacts with the NuRD complex and directs the complex to methylated DNA. NuRD may provide a means of gene silencing by DNA methylation. (+info)Functional analysis of the SIN3-histone deacetylase RPD3-RbAp48-histone H4 connection in the Xenopus oocyte. (3/70)
We investigated the protein associations and enzymatic requirements for the Xenopus histone deacetylase catalytic subunit RPD3 to direct transcriptional repression in Xenopus oocytes. Endogenous Xenopus RPD3 is present in nuclear and cytoplasmic pools, whereas RbAp48 and SIN3 are predominantly nuclear. We cloned Xenopus RbAp48 and SIN3 and show that expression of RPD3, but not RbAp48 or SIN3, leads to an increase in nuclear and cytoplasmic histone deacetylase activity and transcriptional repression of the TRbetaA promoter. This repression requires deacetylase activity and nuclear import of RPD3 mediated by a carboxy-terminal nuclear localization signal. Exogenous RPD3 is not incorporated into previously described oocyte deacetylase and ATPase complexes but cofractionates with a component of the endogenous RbAp48 in the oocyte nucleus. We show that RPD3 associates with RbAp48 through N- and C-terminal contacts and that RbAp48 also interacts with SIN3. Xenopus RbAp48 selectively binds to the segment of the N-terminal tail immediately proximal to the histone fold domain of histone H4 in vivo. Exogenous RPD3 may be targeted to histones through interaction with endogenous RbAp48 to direct transcriptional repression of the Xenopus TRbetaA promoter in the oocyte nucleus. However, the exogenous RPD3 deacetylase functions to repress transcription in the absence of a requirement for association with SIN3 or other targeted corepressors. (+info)SWItched-on mobility. (4/70)
Recent studies have shown that two nucleosome-remodeling complexes, NURF and CHRAC, open chromatin for transcription and replication by using their common catalytic subunit, the nucleosomal ATPase ISWI, to increase the mobility of nucleosomes relative to DNA sequence. (+info)RbAp48 belongs to the histone deacetylase complex that associates with the retinoblastoma protein. (5/70)
The retinoblastoma susceptibility gene product, the Rb protein, is a key regulator of mammalian cell proliferation. One of the major targets of Rb is the S phase inducing E2F transcription factor. Once bound to E2F, Rb represses the expression of E2F-regulated genes. Transcriptional repression by Rb is believed to be crucial for the proper control of cell growth. Recently, we and others showed that Rb represses transcription through the recruitment of a histone deacetylase. Interestingly, we show here that the Rb-associated histone deacetylase complex could deacetylate polynucleosomal substrates, indicating that other proteins could be present within this complex. The Rb-associated protein RbAp48 belongs to many histone deacetylase complexes. We show here that the histone deacetylase HDAC1 is able to mediate the formation of a ternary complex containing Rb and RbAp48. Moreover, less deacetylase activity was found associated with Rb in cell extracts depleted for RbAp48 containing complexes, demonstrating that Rb, histone deacetylase, and RbAp48 are physically associated in live cells. Taken together, these data indicate that RbAp48 is a component of the histone deacetylase complex recruited by Rb. Finally, we found that E2F1 and RbAp48 are physically associated in the presence of Rb and HDAC1, suggesting that RbAp48 could be involved in transcriptional repression of E2F-responsive genes. (+info)Histone binding protein RbAp48 interacts with a complex of CREB binding protein and phosphorylated CREB. (6/70)
A CREB-CREB binding protein (CBP) complex was used as bait to screen a mouse embryo cDNA library in yeast. One of the strongest interactions identified the histone binding protein RbAp48. RbAp48 also interacted weakly with CBP alone but did not interact with phosphorylated or nonphosphorylated CREB. CBP (or its homologue p300) from HeLa cell nuclear extracts coimmunoprecipitated with RbAp48 and its homologue RbAp46 and bound to a glutathione S-transferase-RbAp48 fusion protein. This interaction was stimulated by the addition of phosphorylated CREB and allowed the association of core histones and mononucleosomes in an acetylation-dependent manner. RbAp48 lowered the K(m) of CBP histone acetylase activity and facilitated p300-mediated in vitro transcription of a chromatinized template in the presence of acetylcoenzyme A. These data indicate that the association of phosphorylated CREB with CBP promotes the binding of RbAp48 and its homologue RbAp46, allowing the formation of a complex that facilitates histone acetylation during transcriptional activation. (+info)The histone deacetylase HDAC3 targets RbAp48 to the retinoblastoma protein. (7/70)
The product of the retinoblastoma susceptibility gene, the Rb protein, functions partly through transcriptional repression of E2F-regulated genes. Repression by Rb is mediated, at least in part, by a histone deacetylase complex, whose enzymatic activity relies on HDAC1, HDAC2 or HDAC3. Recently, we have shown that the Rb-associated histone deacetylase complex contains RbAp48 protein, which interacts with HDAC1 and HDAC2. RbAp48 could favour the deacetylation of histones since it binds directly to histone H4. In agreement with that, we show that transcriptional repression of E2F activity requires the presence of RbAp48. HDAC3 was thought not to interact with RbAp48. However, we found that it shared with HDAC1 the ability to favour the recruitment of RbAp48 to Rb. This latter effect was unlikely to be due to activation of Rb function, since HDAC3 did not increase Rb-E2F1 interaction. Rather, we found, surprisingly, that HDAC3 could physically interact with RbAp48 both in vitro and in living cells. Taken together, our data suggest a model in which Rb mediates the recruitment to E2F-regulating promoters of a repressive complex containing either HDAC1, HDAC2 or HDAC3 and the histone-binding protein RbAp48. (+info)Interaction between the Drosophila CAF-1 and ASF1 chromatin assembly factors. (8/70)
The assembly of newly synthesized DNA into chromatin is essential for normal growth, development, and differentiation. To gain a better understanding of the assembly of chromatin during DNA synthesis, we identified, cloned, and characterized the 180- and 105-kDa polypeptides of Drosophila chromatin assembly factor 1 (dCAF-1). The purified recombinant p180+p105+p55 dCAF-1 complex is active for DNA replication-coupled chromatin assembly. Furthermore, we have established that the putative 75-kDa polypeptide of dCAF-1 is a C-terminally truncated form of p105 that does not coexist in dCAF-1 complexes containing the p105 subunit. The analysis of native and recombinant dCAF-1 revealed an interaction between dCAF-1 and the Drosophila anti-silencing function 1 (dASF1) component of replication-coupling assembly factor (RCAF). The binding of dASF1 to dCAF-1 is mediated through the p105 subunit of dCAF-1. Consistent with the interaction between dCAF-1 p105 and dASF1 in vitro, we observed that dASF1 and dCAF-1 p105 colocalized in vivo in Drosophila polytene chromosomes. This interaction between dCAF-1 and dASF1 may be a key component of the functional synergy observed between RCAF and dCAF-1 during the assembly of newly synthesized DNA into chromatin. (+info)Retinoblastoma-Binding Protein 2 (RBP2) is a protein that is encoded by the EZH2 gene in humans. It is a core component of the Polycomb Repressive Complex 2 (PRC2), which is a multi-subunit protein complex involved in the epigenetic regulation of gene expression through histone modification. Specifically, RBP2/EZH2 functions as a histone methyltransferase that trimethylates lysine 27 on histone H3 (H3K27me3), leading to transcriptional repression of target genes. Retinoblastoma-Binding Protein 2 was so named because it was initially identified as a protein that interacts with the retinoblastoma protein (pRb), a tumor suppressor that regulates cell cycle progression and differentiation. However, its role in the development of retinoblastoma or other cancers is not well understood.
Retinoblastoma binding proteins (RBPs) are a group of proteins that interact and bind with the retinoblastoma protein (pRb), which is a tumor suppressor protein. The pRb plays a crucial role in regulating the cell cycle, and its function is often disrupted in various types of cancer, including retinoblastoma.
RBPs can modulate the activity of pRb, either by enhancing or inhibiting its ability to control the cell cycle. Some RBPs may promote the association of pRb with other regulatory proteins, while others may interfere with these interactions. By doing so, RBPs can influence the ability of pRb to regulate gene transcription, DNA replication, and cell cycle progression.
There are several known RBPs, including E2F family transcription factors, DP proteins, and members of the Pocket Protein family (p107 and p130). The interactions between pRb and its binding partners are critical for maintaining normal cell growth and differentiation, and dysregulation of these interactions can contribute to tumor development and progression.
Understanding the roles of RBPs in regulating pRb function is an active area of research, as it may provide insights into the development of new therapies for treating retinoblastoma and other types of cancer.
Retinoblastoma is a rare type of eye cancer that primarily affects young children, typically developing in the retina (the light-sensitive tissue at the back of the eye) before the age of 5. This malignancy originates from immature retinal cells called retinoblasts and can occur in one or both eyes (bilateral or unilateral).
There are two main types of Retinoblastoma: heritable and non-heritable. The heritable form is caused by a genetic mutation that can be inherited from a parent or may occur spontaneously during embryonic development. This type often affects both eyes and has an increased risk of developing other cancers. Non-heritable Retinoblastoma, on the other hand, occurs due to somatic mutations (acquired during life) that affect only the retinal cells in one eye.
Symptoms of Retinoblastoma may include a white pupil or glow in photographs, crossed eyes, strabismus (misalignment of the eyes), poor vision, redness, or swelling in the eye. Treatment options depend on various factors such as the stage and location of the tumor(s), patient's age, and overall health. These treatments may include chemotherapy, radiation therapy, laser therapy, cryotherapy (freezing), thermotherapy (heating), or enucleation (removal of the affected eye) in advanced cases.
Early detection and prompt treatment are crucial for improving the prognosis and preserving vision in children with Retinoblastoma. Regular eye examinations by a pediatric ophthalmologist or oncologist are recommended to monitor any changes and ensure timely intervention if necessary.
Retinoblastoma Protein (pRb or RB1) is a tumor suppressor protein that plays a critical role in regulating the cell cycle and preventing uncontrolled cell growth. It is encoded by the RB1 gene, located on chromosome 13. The retinoblastoma protein functions as a regulatory checkpoint in the cell cycle, preventing cells from progressing into the S phase (DNA synthesis phase) until certain conditions are met.
When pRb is in its active state, it binds to and inhibits the activity of E2F transcription factors, which promote the expression of genes required for DNA replication and cell cycle progression. Phosphorylation of pRb by cyclin-dependent kinases (CDKs) leads to the release of E2F factors, allowing them to activate their target genes and drive the cell into S phase.
Mutations in the RB1 gene can result in the production of a nonfunctional or reduced amount of pRb protein, leading to uncontrolled cell growth and an increased risk of developing retinoblastoma, a rare form of eye cancer, as well as other types of tumors.
Retinal neoplasms are abnormal growths or tumors that develop in the retina, which is the light-sensitive tissue located at the back of the eye. These neoplasms can be benign or malignant and can have varying effects on vision depending on their size, location, and type.
Retinal neoplasms can be classified into two main categories: primary and secondary. Primary retinal neoplasms originate from the retina or its surrounding tissues, while secondary retinal neoplasms spread to the retina from other parts of the body.
The most common type of primary retinal neoplasm is a retinoblastoma, which is a malignant tumor that typically affects children under the age of five. Other types of primary retinal neoplasms include capillary hemangioma, cavernous hemangioma, and combined hamartoma of the retina and RPE (retinal pigment epithelium).
Secondary retinal neoplasms are usually metastatic tumors that spread to the eye from other parts of the body, such as the lung, breast, or skin. These tumors can cause vision loss, eye pain, or floaters, and may require treatment with radiation therapy, chemotherapy, or surgery.
It is important to note that retinal neoplasms are relatively rare, and any symptoms or changes in vision should be evaluated by an ophthalmologist as soon as possible to rule out other potential causes and develop an appropriate treatment plan.
Retinoblastoma genes, often referred to as RB1, are tumor suppressor genes that play a critical role in regulating cell growth and division. When functioning properly, these genes help prevent the development of cancer by ensuring that cells divide and grow in a controlled manner.
Mutations in the Retinoblastoma gene can lead to retinoblastoma, a rare type of eye cancer that typically affects young children. There are two types of retinoblastoma: hereditary and non-hereditary. Hereditary retinoblastoma is caused by an inherited mutation in the RB1 gene, while non-hereditary retinoblastoma is caused by a mutation that occurs spontaneously during development.
When both copies of the RB1 gene are mutated or inactivated in a retinal cell, it can lead to uncontrolled cell growth and division, resulting in the formation of a tumor. Symptoms of retinoblastoma may include an unusual white pupil reflex, crossed eyes, or a lazy eye. If left untreated, retinoblastoma can spread to other parts of the body and be life-threatening.
It is important to note that mutations in the RB1 gene can also increase the risk of developing other types of cancer, such as lung, breast, and bladder cancer, later in life.
Eye neoplasms, also known as ocular tumors or eye cancer, refer to abnormal growths of tissue in the eye. These growths can be benign (non-cancerous) or malignant (cancerous). Eye neoplasms can develop in various parts of the eye, including the eyelid, conjunctiva, cornea, iris, ciliary body, choroid, retina, and optic nerve.
Benign eye neoplasms are typically slow-growing and do not spread to other parts of the body. They may cause symptoms such as vision changes, eye pain, or a noticeable mass in the eye. Treatment options for benign eye neoplasms include monitoring, surgical removal, or radiation therapy.
Malignant eye neoplasms, on the other hand, can grow and spread rapidly to other parts of the body. They may cause symptoms such as vision changes, eye pain, floaters, or flashes of light. Treatment options for malignant eye neoplasms depend on the type and stage of cancer but may include surgery, radiation therapy, chemotherapy, or a combination of these treatments.
It is important to note that early detection and treatment of eye neoplasms can improve outcomes and prevent complications. Regular eye exams with an ophthalmologist are recommended for early detection and prevention of eye diseases, including eye neoplasms.
Retinoblastoma protein