Death-signal-induced relocalization of cyclin-dependent kinase 11 to mitochondria.

Abstract

Fas receptor-Fas ligand interaction appears to be important in carcinogenesis, tumour outgrowth and metastasis. Emerging evidence suggests that CDK11 (cyclin-dependent kinase 11) plays a role in apoptosis and melanoma development. Here, we show that CDK11p110 protein kinase was cleaved after induction of apoptosis by Fas. The N-terminal portion of CDK11p110, CDK11p60, was translocated from the nucleus to the mitochondria. The targeting of CDK11p60 to mitochondria occurred as early as 12 h after treatment. Overexpression of EGFP (enhanced green fluorescent protein)-tagged CDK11p60 could partially break down the mitochondrial membrane potential, induce cytochrome c release and promote apoptosis. Reduction of endogenous CDK11p110 protein levels with siRNA (small interfering RNA) resulted in the suppression of both cytochrome c release and apoptosis. In addition, subcellular fractionation studies of Fas-mediated apoptosis demonstrated that CDK11p60 was associated with the mitochondrial import motor, mitochondrial heat shock protein 70. Taken together, our data suggest that CDK11p60 can contribute to apoptosis by direct signalling at the mitochondria, thereby amplifying Fas-induced apoptosis in melanoma cells.

• Authors: Yongmei Feng, Maria E Ariza, Anne-Christine Goulet, Jiaqi Shi, Mark A Nelson
• Journal: The Biochemical journal (Biochem J) Vol. 392 Issue Pt 1 Pg. 65-73 (Nov 15 2005) ISSN: 1470-8728 [Electronic] England
• PMID: 16004605 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• fas Receptor
• CDK11a protein, human
• Cyclin-Dependent Kinases

Topics

• Apoptosis (physiology)
• Cell Line, Tumor
• Cell Nucleus (enzymology, metabolism)
• Cyclin-Dependent Kinases (metabolism)
• Humans
• Mitochondria (enzymology, metabolism)
• Protein Transport
• RNA Interference
• Signal Transduction
• fas Receptor (metabolism)