_CG-SLENP: A Chemical Genetics Strategy To Selectively Label Existing Proteins and Newly Synthesized Proteins

Area of Science:

• Cell Biology
• Chemical Biology
• Molecular Biology

Background:

• Accurate protein synthesis and localization are crucial for cellular function.
• Distinguishing newly synthesized proteins from existing ones is vital for understanding cellular processes but lacks effective methods.

Purpose of the Study:

• To develop a novel chemical genetics-based approach for the selective labeling of existing and newly synthesized proteins.
• To investigate potential differences between newly synthesized and existing lamin A (LA) using this new method.

Main Methods:

• Introduced the chemical genetics-selective labeling of existing and newly synthesized proteins (CG-SLENP) method.
• Utilized HaloTag in-frame fusion with lamin A (LA) for selective protein labeling in living cells.
• Employed a selective small molecule ligand (LBL1) to probe differential properties of LA pools.

Main Results:

• Demonstrated successful selective labeling of both existing and newly synthesized LA pools using CG-SLENP in living cells.
• Showed that LBL1 differentially modulates newly synthesized and existing LA.
• Provided evidence that newly synthesized LA exhibits distinct assembly states compared to existing LA.

Conclusions:

• The CG-SLENP method offers a groundbreaking approach for distinguishing protein populations in living cells.
• Newly synthesized lamin A has distinct assembly states from existing lamin A.
• The CG-SLENP technique is potentially applicable to studying a wide range of cellular proteins.