p62, a phosphotyrosine independent ligand of SH2 domain of p56^lck, is cleaved by caspase‐3 during apoptosis in Jurkat cells

p62 is a phosphotyrosine‐independent ligand of the SIC domain of p56^lck, a T‐cell specific Src family tyrosine kinase. Recently p62 has been shown to interact with a number of proteins, such as PKCζ and ubiquitin, and implicated in important cellular functions such as cell proliferation. Since the two p62 interacting proteins, p56^lck and PKCζ, have been reported to play roles in cell death, I have addressed the potential role of p62 during apoptosis in Jurkat cells in this study. Herein I show that p62 was specifically cleaved into two peptides by a caspase‐3‐like activity during Fas‐receptor mediated apoptosis in Jurkat cells. This cleavage generated two fragments with molecular weights of about 35 kDa that differed in subcellular localizations. The N‐terminal cleaved fragment was present in the detergent‐insoluble fraction whereas the C‐terminal fragment was found in the detergent‐soluble fraction. In addition, the C‐terminal fragment appeared to be subjected to further degradation as apoptosis prolonged. Moreover, overexpression of p62 in Jurkat cells attenuated the Fas receptor mediated apoptosis, suggesting that p62 is involved in apoptotic signal transduction pathway in lymphocytes.

Key words:

• p62
• Caspase‐3
• Fas
• Apoptosis
• Cleavage
• Jurkat cells

Notes

To whom correspondence should be addressed. Tel: [phone], Fax: [phone], E‐mail: [email protected]