Retinoblastoma-like protein 2

Retinoblastoma-like protein 2 (RBL2), also known as p130, is a tumor suppressor protein that plays a crucial role in regulating cell cycle progression and cell differentiation. It is a member of the retinoblastoma protein (Rb) family, which also includes Rb and p107. RBL2 is involved in various cellular processes, including cell cycle arrest, DNA replication, and chromatin remodeling.

Structure and Function

RBL2 is a large protein consisting of 1139 amino acids. It contains several functional domains, including an N-terminal domain, a pocket domain, and a C-terminal domain. The pocket domain is responsible for interacting with various cellular proteins, such as E2F transcription factors, histone deacetylases, and cyclin-dependent kinases (CDKs). These interactions allow RBL2 to regulate gene expression and control cell cycle progression.

RBL2 functions as a tumor suppressor by inhibiting cell proliferation and promoting cell differentiation. It acts as a negative regulator of the cell cycle by binding to E2F transcription factors and preventing their activation of genes required for cell cycle progression. RBL2 also recruits histone deacetylases to chromatin, leading to the repression of genes involved in cell proliferation. Additionally, RBL2 interacts with CDKs, inhibiting their kinase activity and preventing cell cycle progression.

Role in Cancer

Mutations or dysregulation of RBL2 have been implicated in various types of cancer. Loss of RBL2 function can lead to uncontrolled cell proliferation and tumor formation. Inactivation of RBL2 has been observed in several cancer types, including breast cancer, lung cancer, and bladder cancer. Furthermore, RBL2 is frequently downregulated in aggressive tumors and is associated with poor prognosis.

Clinical Significance

The study of RBL2 has important clinical implications. Its dysregulation in cancer suggests that it could serve as a potential therapeutic target. Restoring RBL2 function or targeting its downstream effectors could potentially inhibit tumor growth and improve patient outcomes. Additionally, RBL2 expression levels could serve as a prognostic marker for certain cancers, helping to predict patient survival and guide treatment decisions.

See Also

• Retinoblastoma protein
• p107 (protein)

References

1. Cobrinik D. Pocket proteins and cell cycle control. Oncogene. 2005;24(17):2796-2809. doi:10.1038/sj.onc.1208619 2. Classon M, Harlow E. The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer. 2002;2(12):910-917. doi:10.1038/nrc950 3. Harbour JW, Dean DC. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 2000;14(19):2393-2409. doi:10.1101/gad.813200