Protein degradation, dephosphorylation, or denaturation occurs when samples are kept above 4°C throughout the protocol, resulting in high background or loss of target bands.
Common Causes
1Lysates or samples not kept on ice during preparation and handling
2Prolonged exposure to temperatures above 4°C activating proteases and phosphatases
3Lack of protease inhibitors in lysis buffer
Solutions
1Ensure all lysates and samples are kept on ice throughout preparation and handling
2Work quickly and maintain samples at 4°C or below during all protocol steps
3Add protease inhibitors to lysis buffer; load at least 20–30 µg protein per lane to ensure sufficient target