- Elongin B is a small, ubiquitously expressed protein that functions as a regulatory and adaptor subunit in multiple multiprotein complexes.
- It is encoded by the ELOB gene and belongs to the ubiquitin-like protein family, reflecting its structural similarity to ubiquitin.
- Despite this similarity, elongin B does not function as a classical ubiquitin modifier; instead, it serves primarily as a scaffold or adaptor protein, stabilizing protein–protein interactions within complexes that regulate transcription elongation and ubiquitin-mediated protein degradation. Its versatility and widespread presence make elongin B an important regulatory hub in cellular processes that control gene expression and protein turnover.
- One of the central roles of elongin B is within the Elongin complex, which consists of elongin A, elongin B, and elongin C. In this trimeric complex, elongin A is the catalytic subunit responsible for stimulating RNA polymerase II transcription elongation, while elongins B and C form a stable heterodimer that binds elongin A and stabilizes its activity. Through this interaction, elongin B indirectly promotes efficient transcription by helping elongin A overcome RNA polymerase II pausing during elongation. This activity is crucial for genes that require high transcriptional output, as it ensures rapid and continuous synthesis of messenger RNA.
- Elongin B also plays a vital role in the assembly of the von Hippel–Lindau (VHL) E3 ubiquitin ligase complex, also known as the VBC-CUL2-Rbx1 complex. In this setting, elongin B and elongin C act as adaptor proteins that link the VHL tumor suppressor protein to the Cullin-2 scaffold. Together with Rbx1, this forms a functional E3 ligase that targets specific substrates, most notably hypoxia-inducible factor alpha (HIF-α), for ubiquitination and subsequent proteasomal degradation under normoxic conditions. By contributing to the stability and integrity of this complex, elongin B indirectly regulates cellular oxygen-sensing pathways, angiogenesis, and metabolism. The functional connection of elongin B to VHL and HIF signaling underscores its importance in tumor suppression and hypoxia adaptation.
- Structurally, elongin B is characterized by its ubiquitin-like fold, which enables it to participate in diverse protein–protein interactions. It lacks catalytic activity on its own, but its ability to stabilize interactions within multiprotein complexes makes it indispensable for the activity of its partners. This structural versatility also explains why elongin B is a shared component of both transcriptional and ubiquitin ligase complexes, reflecting its role as a multifunctional adaptor.
- From a biomedical perspective, elongin B is significant because of its links to cancer biology. Mutations or dysfunction in the VHL tumor suppressor pathway, where elongin B plays a structural role, are central to the development of clear cell renal cell carcinoma and other cancers. While elongin B itself is not typically mutated, its function is required for the integrity of the VHL–Cullin–E3 ligase complex. In this way, elongin B acts as a “silent partner” whose loss of function or destabilization could disrupt protein degradation pathways and contribute to disease progression. Beyond cancer, elongin B’s role in transcription elongation suggests it may also influence gene expression changes during stress, inflammation, or development, although these roles are less well characterized.
