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What is the role of the retinoblastoma protein in cell-cycle regulation? Is the retinoblastoma gene a tumor-suppressor gene or an oncogene?

Short Answer

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Short Answer: The retinoblastoma protein (Rb) regulates cell-cycle progression, particularly at the G1-S phase checkpoint, by acting as a gatekeeper to prevent cells from entering the S phase under inappropriate conditions. The retinoblastoma gene (RB1) is a tumor-suppressor gene, as its mutation or inactivation can lead to uncontrolled cell growth and increased risk of cancer development, such as retinoblastoma.

Step by step solution

01

Understanding the Cell Cycle

The cell cycle is a series of events that lead to cell growth, replication, and eventually division into two daughter cells. It consists of different phases, such as the G1 phase, S phase, G2 phase, and the M phase (mitosis). The regulation of the cell cycle is essential to ensure proper cell division, growth, and reduced risk of damaged or mutated cellular components and DNA.
02

Retinoblastoma Protein (Rb) and its Role in Cell-cycle Regulation

The retinoblastoma protein (Rb) is a crucial protein responsible for controlling cell-cycle progression, particularly at the G1-S phase checkpoint. Rb acts as a gatekeeper, preventing the cell from advancing into the S phase if conditions are not ideal for DNA replication. Rb binds to transcription factors, such as E2F, to inhibit their activity and prevent the cell from proceeding to the S phase. When the cell receives appropriate signals for cell growth and proliferation, Rb is inactivated through phosphorylation by cyclin-dependent kinases (CDKs). This inactivation releases E2F, which can now activate genes necessary for DNA replication and cell-cycle progression.
03

Oncogenes and Tumor-Suppressor Genes

There are two major classes of genes involved in cancer development when mutated: oncogenes and tumor-suppressor genes. Oncogenes promote cell growth and division when activated, potentially leading to uncontrolled growth and formation of tumors. Tumor-suppressor genes, on the other hand, function to regulate cell division and prevent abnormal cell proliferation. When tumor-suppressor genes are inactivated or lost, cells can grow uncontrollably, increasing the risk of cancer development.
04

Retinoblastoma Gene: Tumor-Suppressor Gene or Oncogene?

The retinoblastoma gene (RB1) is a tumor-suppressor gene. It encodes the retinoblastoma protein (Rb) which, as discussed above, plays a crucial role in regulating cell-cycle progression. When the RB1 gene is mutated or inactivated, the Rb protein's function as a gatekeeper is compromised, leading to uncontrolled cell growth and increased risk of cancer development. Specifically, RB1 mutations can lead to retinoblastoma, a rare type of eye cancer in children. In conclusion, the retinoblastoma protein plays a vital role in controlling cell-cycle progression, and the retinoblastoma gene is classified as a tumor-suppressor gene because its mutation or inactivation can lead to uncontrolled cell growth and potential cancer development.

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Most popular questions from this chapter

Compare familial and sporadic retinoblastomas in terms of genetics and age of onset. Is it possible to distinguish between these two using genetic tests? Consider the number of mutations required, loss of heterozygosity, and the two-hit hypothesis.

How does the environment contribute to cancer?

In this chapter, we focused on cancer as a genetic disease, with an emphasis on the relationship between cancer, the cell cycle, and DNA damage, as well as on the multiple steps that lead to cancer. (a) How do we know that malignant tumors arise from a single cell that contains mutations? (b) How do we know that cancer development requires more than one mutation? (c) How do we know that cancer cells contain defects in DNA repair?

Those who inherit a mutant allele of the \(R B 1\) gene are at risk for developing a bone cancer called osteosarcoma. You suspect that in these cases, osteosarcoma requires a mutation in the second \(R B 1\) allele, and you have cultured some osteosarcoma cells and obtained a cDNA clone of a normal human \(R B I\) gene. A colleague sends you a research paper revealing that a strain of cancer-prone mice develop malignant tumors when injected with osteosarcoma cells, and you obtain these mice. Using these three resources, what experiments would you perform to determine (a) whether osteosarcoma cells carry two \(R B 1\) mutations, (b) whether osteosarcoma cells produce any \(\mathrm{pRB}\) protein, and (c) if the addition of a normal \(R B 1\) gene will change the cancer-causing notential of astensarcama cells?

A study by Bose and colleagues (1998. Blood 92: \(3362-3367\) ) and a previous study by Biernaux and others (1996. Bone Marrow Transplant 17: (Suppl.3) \(\mathrm{S} 45-\mathrm{S} 47\) ) showed that \(B C R-A B L\) fusion gene transcripts can be detected in 25 to 30 percent of healthy adults who do not develop chronic myelogenous leukemia (CML). Explain how these individuals can carry a fusion gene that is transcriptionally active and yet do not develop CML.

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