Related Experiment Video
Updated: Jun 16, 2025
09:40
In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
Published on: November 2, 2017
7.3K
Sumo-regulatory SENP2 controls the homeostatic squamous mitosis-differentiation checkpoint
Jesús Galán-Vidal1, Lorena García-Gaipo1, Rut Molinuevo1
1Cell cycle, Stem Cell Fate and Cancer Laboratory, Institute for Research Marqués de Valdecilla (IDIVAL), 39011, Santander, Spain.
Cell Death & Disease
|August 16, 2024
Summary
SENP2, a SUMO regulatory protein, controls epithelial cell differentiation by regulating the mitotic spindle. Loss of SENP2 promotes differentiation and correlates with PD-L1 in lung cancer, suggesting its potential as a biomarker.
Area of Science:
- Cell Biology
- Cancer Biology
- Molecular Biology
Background:
- Squamous cell carcinoma frequently occurs in the lung's non-epidermoid epithelium through unclear mechanisms.
- A poorly understood mitotic checkpoint drives cells with genetic damage into epidermoid differentiation.
Purpose of the Study:
- To identify novel regulators of the epithelial mitosis-differentiation checkpoint.
- To investigate the role of the SUMO regulatory protein SENP2 in this process.
Main Methods:
- RNA sequencing to identify potential regulators.
- SENP2 silencing using specific shRNAs in primary human epidermal cells.
- Analysis of mitotic entry, exit, and chromosomal alignment.
- Correlation analysis with PD-L1 expression in lung carcinomas.
Main Results:
- SENP2 is localized to mitotic spindles in human epidermal cells.
- SENP2 silencing induced rapid differentiation and mitotic defects, including delayed entry/exit and chromosomal misalignment.
- SENP2 expression inversely correlated with PD-L1 in aggressive lung carcinomas.
- Metastatic head and neck cancer cells resistant to checkpoint activation were also resistant to SENP2 depletion.
Conclusions:
- SENP2 is a crucial regulator of the epithelial mitosis-differentiation checkpoint, acting via the mitotic spindle.
- SENP2 may serve as a potential biomarker in epithelial cancers, particularly lung cancer, due to its inverse correlation with PD-L1.
Related Concept Videos
01:14Maintenance of the ES Cell State
2.2K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.2K
02:23Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
01:28The Cell Cycle Control System
2.7K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
2.7K
02:19The Spindle Assembly Checkpoint
3.1K
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.1K
02:36Cells Coordinate Growth and Proliferation
4.5K
Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...
4.5K
01:23Negative Regulator Molecules
35.2K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.2K