The Role of the SCF Complex In The Cell Cycle

NewsGuard 100/100 Score

SCF complexes are a class of E3 ubiquitination ligase that facilitate proteasomal degradation through the catalysis of ubiquitinylation. The cell cycle relies on ubiquitin and the SCF complex plays an integral role in the regulation of this process.

Cell undergoing cytokinesis, the final stage of the cell cycle - By Roberto Piras

Roberto Piras | Shutterstock

Ubiquitin ligase also regulates ubiquitinylation by stimulating the degradation of cell cycle proteins via the 26S proteasome. Dysregulation of this process can result in the progressive transformation of normal cells into cancer cells.

The Cell Cycle

Cell division (mitosis) occurs through the following phases, each of which is characterized by unique events.

  1. G1 phase
  2. S phase
  3. G2 phase
  4. M phase

In a somatic (body) cell, the cell cycle takes roughly 24 hours to completes, starting with G1. In G1, cells become enlarged, mRNA and new proteins are synthesized, and these are then used during the subsequent synthesis of DNA. DNA replication begins in S phase and requires between 10 and 12 hours to complete. DNA and protein synthesis continue throughout G2 phase. These three stages constitute interphase.

Quiescent and aging cells which are unable to replicate are said to be in resting phase or G0 where they might stay for an indefinite length of time. The process of mitosis takes place during M or mitotic phase where the chromosomes are separated into two nuclei and cytokinesis takes place.

cell cycle control

Structure of the SCF complex

The structure of SCF ligases are variable due to the F-box protein (FBP) which determines the substrate specificity of SCF complex.  FBPs mediate protein-protein interaction with roughly 50 amino acids within their structural motifs. There are approximately 70 different FBPs found in mammals.

S-Phase Kinase Associated Protein 2 (Skp2), an FBP involved in cell cycle regulation, is one of the most highly studied FBPs. Characterised by its leucine rich repeats, Skp2 belongs to the FBXL class of FBPs. There have three components: RING box protein 1 (Rbx1/Roc1, a ring-finger protein), S-Phase Kinase Associated Protein 1 (Skp1, an adaptor protein), and Cullin1 (Cul1, a scaffold protein). FBPs like Skp2 bind directly to the adaptor protein, Skp1, via an F-box motif.

Function of the SCF complex

The Cul1/Rbx1 components of the SCF complex work synergistically to catalyse the transfer of ubiquitin from E2 ubiquitin-conjugating enzymes. However, this complex requires activation by a protein called NEDD8. During interphase, a range of proteins bind to the SCF complex and begin to degrade.

At G1, retinoblastoma-like protein 2 is ubiquitinated. Other proteins, including CDC25A, p27KIP1, Cyclin E and Cdt1 are phosphorylated between the G1 and S by CDK2 which bind to the SCF complex. This prompts their subsequent degradation. As the cell cycle enters the mitotic stage, Wee1 (a G2 checkpoint kinase), is degraded alongside Emi1 (an early mitotic inhibitor) when bound to the SCF complex.

Further Reading

Last Updated: Jul 22, 2023

Maryam Mahdi

Written by

Maryam Mahdi

Maryam is a science writer with a passion for travel. She graduated in 2012 with a degree in Biomedical Sciences (B.Sc.) from the University of Manchester. Maryam previously worked in scientific education and has produced articles, videos, and presentations to highlight the association between dietary choices and cancer. She produces a range of articles for News-Medical, with a focus on microbiology and microscopy.


Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Mahdi, Maryam. (2023, July 22). The Role of the SCF Complex In The Cell Cycle. News-Medical. Retrieved on May 24, 2024 from

  • MLA

    Mahdi, Maryam. "The Role of the SCF Complex In The Cell Cycle". News-Medical. 24 May 2024. <>.

  • Chicago

    Mahdi, Maryam. "The Role of the SCF Complex In The Cell Cycle". News-Medical. (accessed May 24, 2024).

  • Harvard

    Mahdi, Maryam. 2023. The Role of the SCF Complex In The Cell Cycle. News-Medical, viewed 24 May 2024,


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Investigating the evolution of cell division mechanisms in Ichthyosporea