bladder cancer Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations that turn off (inactivate) the RB1 gene have been reported in some cases of bladder cancer. Mutations in RB1 are thought to contribute to the development of bladder cancer, and these genetic changes may help predict whether tumors will grow rapidly and spread to other tissues. retinoblastoma Hundreds of mutations in the RB1 gene have been identified in people with retinoblastoma, a rare type of eye cancer that typically affects young children. This cancer develops in the retina, which is the specialized light-sensitive tissue at the back of the eye that detects light and color. Researchers estimate that 40 percent of all retinoblastomas are germinal, which means that RB1 mutations occur in all of the body's cells and can be passed to the next generation. The other 60 percent are non-germinal, which means that RB1 mutations occur only in the eye and cannot be passed to the next generation. In germinal retinoblastoma, an RB1 mutation is present in all of the body's cells. For retinoblastoma to develop, the other copy of the RB1 gene also must be mutated or lost. This second mutation typically occurs early in life in retinal cells. Cells with two altered copies of the RB1 gene produce no functional pRB and are unable to regulate cell division effectively. As a result, retinal cells lacking functional pRB can divide uncontrollably to form cancerous tumors. Some studies suggest that additional genetic changes can influence the development of retinoblastoma; these changes may help explain variations in the development and growth of tumors in different people. In people with germinal retinoblastoma, RB1 mutations increase the risk of several other cancers outside the eye. Specifically, these people are more likely to develop a cancer of the pineal gland in the brain (pinealoma), a type of bone cancer known as osteosarcoma, cancers of soft tissues such as muscle, and an aggressive form of skin cancer called melanoma. Non-germinal retinoblastoma occurs in people with no history of the disorder in their family. Affected individuals are born with two normal copies of the RB1 gene. Then, usually in early childhood, both copies of the gene in retinal cells acquire mutations or are lost. These genetic changes prevent the cells from producing any functional pRB. The loss of this protein allows retinal cells to grow and divide without control or order, leading to the development of a cancerous tumor. other cancers In addition to bladder cancer, somatic mutations in the RB1 gene are associated with many other types of cancer. For example, changes in the RB1 gene have been reported in some cases of lung cancer, breast cancer, a bone cancer known as osteosarcoma, and an aggressive form of skin cancer called melanoma. Somatic RB1 mutations have also been identified in some leukemias, which are cancers of blood-forming cells. Somatic RB1 mutations in cancer cells inactivate pRB so it can no longer regulate cell division effectively.

     The RB1 gene provides instructions for making a protein called pRB. This protein acts as a tumor suppressor, which means that it regulates cell growth and keeps cells from dividing too fast or in an uncontrolled way. Under certain conditions, pRB stops other proteins from triggering DNA replication, the process by which DNA makes a copy of itself. Because DNA replication must occur before a cell can divide, tight regulation of this process controls cell division and helps prevent the growth of tumors. Additionally, pRB interacts with other proteins to influence cell survival, the self-destruction of cells (apoptosis), and the process by which cells mature to carry out special functions (differentiation).

The following transcription factors affect gene expression:

• p53
• CREB
• deltaCREB
• E2F-1
• E2F-4
• YY1

Tissue specificity:

Expressed in the retina.

Molecular Function:

• Core Promoter Binding
• Dna Binding
• Transcription Factor Activity, Sequence-Specific Dna Binding
• Transcription Coactivator Activity
• Transcription Factor Binding
• Kinase Binding
• Ubiquitin Protein Ligase Binding
• Identical Protein Binding
• Androgen Receptor Binding
• Phosphoprotein Binding

Biological Processes:

• Cell Cycle Checkpoint
• G1/S Transition Of Mitotic Cell Cycle
• Regulation Of Transcription Involved In G1/S Transition Of Mitotic Cell Cycle
• Regulation Of Cell Growth
• Tissue Homeostasis
• Chromatin Remodeling
• Transcription, Dna-Templated
• Negative Regulation Of Protein Kinase Activity
• Cell Cycle Arrest
• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter During Mitotic Cell Cycle
• Mitotic Cell Cycle Checkpoint
• Ras Protein Signal Transduction
• Regulation Of Mitotic Cell Cycle
• Negative Regulation Of Gene Expression
• Viral Process
• Covalent Chromatin Modification
• Androgen Receptor Signaling Pathway
• Sister Chromatid Biorientation
• Neuron Projection Development
• Maintenance Of Mitotic Sister Chromatid Cohesion
• Glial Cell Apoptotic Process
• Skeletal Muscle Cell Differentiation
• Neuron Maturation
• Enucleate Erythrocyte Differentiation
• Negative Regulation Of Sequence-Specific Dna Binding Transcription Factor Activity
• Regulation Of Lipid Kinase Activity
• Myoblast Differentiation
• Positive Regulation Of Macrophage Differentiation
• Positive Regulation Of Mitotic Metaphase/Anaphase Transition
• Negative Regulation Of Smoothened Signaling Pathway
• Negative Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Digestive Tract Development
• Cell Morphogenesis Involved In Neuron Differentiation
• Negative Regulation Of Epithelial Cell Proliferation
• Striated Muscle Cell Differentiation
• Cell Division
• Neuron Apoptotic Process
• Protein Localization To Chromosome, Centromeric Region
• Cellular Response To Xenobiotic Stimulus
• Regulation Of Cohesin Loading
• Negative Regulation Of Transcription Involved In G1/S Transition Of Mitotic Cell Cycle
• Regulation Of Centromere Complex Assembly
• Hepatocyte Apoptotic Process
• Negative Regulation Of G1/S Transition Of Mitotic Cell Cycle
• Positive Regulation Of Transcription Regulatory Region Dna Binding

Drug Bank:

• Insulin Regular