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Binding of CDK9 to TRAF2
T K MacLachlan1, N Sang, A De Luca
1Sbarro Institute for Cancer Research and Molecular Medicine, Department of Pathology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abstract:
CDK9 has been recently shown to have increased kinase activity in differentiated cells in culture and a differentiated tissue-specific expression in the developing mouse. In order to identify factors that contribute to CDK9's differentiation-specific function, we screened a mouse embryonic library in the yeast two-hybrid system and found a tumor necrosis factor signal transducer, TRAF2, to be an interacting protein. CDK9 interacts with a conserved domain in the TRAF-C region of TRAF2, a motif that is known to bind other kinases involved in TRAF-mediated signaling. Endogenous interaction between the two proteins appears to be specific to differentiated tissue. TRAF2-mediated signaling may incorporate additional kinases to signal cell survival in myotubes, a cell type that is severely affected in TRAF2 knockout mice.
Insights
Cyclin-dependent kinase 9 (CDK9) interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2) in differentiated tissues. This interaction may be crucial for cell survival signaling in myotubes.
Area of Science:
- Molecular Biology
- Cell Signaling
- Biochemistry
Background:
- Cyclin-dependent kinase 9 (CDK9) exhibits increased kinase activity and tissue-specific expression in differentiated cells.
- The precise mechanisms regulating CDK9's differentiation-specific functions are not fully understood.
Purpose of the Study:
- To identify proteins interacting with CDK9 and contributing to its differentiation-specific roles.
- To investigate the functional implications of CDK9-interacting proteins in cellular signaling pathways.
Main Methods:
- Yeast two-hybrid screening of a mouse embryonic library to identify CDK9-interacting proteins.
- Analysis of protein-protein interaction domains within identified partners.
- Assessment of endogenous protein interactions in differentiated tissues.
Main Results:
- Tumor necrosis factor receptor-associated factor 2 (TRAF2) was identified as a CDK9-interacting protein.
- CDK9 binds to the conserved TRAF-C domain of TRAF2, a known kinase-binding motif.
- Endogenous interaction between CDK9 and TRAF2 is specific to differentiated tissues.
Conclusions:
- TRAF2 is a novel interacting partner of CDK9, suggesting a role in CDK9-mediated signaling.
- TRAF2-mediated signaling pathways may involve additional kinases like CDK9 to regulate cell survival.
- This interaction is particularly relevant for cell survival in myotubes, a cell type impacted in TRAF2 knockout models.