Related Experiment Video

Updated: Jan 13, 2026

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
11:36

In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones

Published on: July 25, 2019

11.4K

The mechanistic basis and cellular functions of UFMylation

Masaaki Komatsu1,2, Nobuo N Noda3,4, Toshifumi Inada5

  • 1Department of Physiology, Juntendo University Graduate School of Medicine, Tokyo, Japan. mkomatsu@juntendo.ac.jp.

Nature Reviews. Molecular Cell Biology
|January 9, 2026
PubMed

Insights

UFMylation, a key process for endoplasmic reticulum quality control, modifies proteins like RPL26 to protect cells during stress. Its role in proteostasis and disease is expanding, linking ER function to stress responses.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • UFMylation is a ubiquitin-like modification crucial for endoplasmic reticulum-associated quality control (ER-RQC).
  • It involves the conjugation of UFM1 to substrates, such as the 60S ribosomal subunit protein RPL26.
  • This process is vital for maintaining endoplasmic reticulum and ribosomal integrity under cellular stress.

Purpose of the Study:

  • To review the structural and mechanistic basis of UFMylation in ER-RQC.
  • To explore UFMylation's contribution to proteostasis.
  • To discuss the emerging functional breadth and disease relevance of UFMylation.

Main Methods:

  • Literature review focusing on structural and mechanistic studies of UFMylation.
  • Analysis of recent findings on UFM1-modified proteins and their pathways.
  • Synthesis of information on UFMylation's role in cellular stress and disease.

Main Results:

  • UFMylation plays a central role in ER-RQC by modifying key substrates like RPL26.
  • The modification helps maintain cellular integrity under stress conditions.
  • While many UFM1 substrates are identified, their physiological roles require further investigation.

Conclusions:

  • UFMylation is a critical regulatory system connecting ER function to cellular stress responses.
  • Its link to diseases like neurodevelopmental disorders and cancer highlights its biological significance.
  • Further research is needed to clarify the relevance of newly identified UFM1 substrates.

More Related Videos

Expression, Purification, Crystallization, and Enzyme Assays of Fumarylacetoacetate Hydrolase Domain-Containing Proteins10:21

Expression, Purification, Crystallization, and Enzyme Assays of Fumarylacetoacetate Hydrolase Domain-Containing Proteins

Published on: June 20, 2019

24.8K
Dissecting Mechanoenzymatic Properties of Processive Myosins with Ultrafast Force-Clamp Spectroscopy09:38

Dissecting Mechanoenzymatic Properties of Processive Myosins with Ultrafast Force-Clamp Spectroscopy

Published on: July 1, 2021

1.6K

Related Concept Videos

Mechanical Protein Functions01:58

Mechanical Protein Functions

Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force. 
5.5K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.9K
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
3.0K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
8.6K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.2K
Studying the Cytoskeleton01:17

Studying the Cytoskeleton

The cytoskeletal architecture can be studied using different microscopic and biochemical techniques. Electron microscopy was instrumental in discovering the cytoskeletal architecture around the 1960s, which allowed obtaining structural information at a high-resolution level. However, the sample preparation procedure often limits this ability in biological samples. Several protocols have been developed over the years to optimize sample preparation. In one of the protocols known as rotary...
8.5K