A study on PIP5Kalpha degradation by Nedd4-1-mediated ubiquitination

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a critical lipid mediator of diverse membrane processes including vesicle trafficking, actin cytoskeleton dynamics and cell signaling at the cell surface, indicating significance of spatiotemporal regulation and underlying mechanism of PIP2 concentration. So far, most studies on PIP2 generation have focused on how catalytic activities of the type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family members, the major PIP2-producing enzymes, are regulated, but little information is available on PIP2 control by protein stability and expression level of PIP5K. Hence, we have examined whether PIP5K is ubiquitinated working as another route for such a regulatory pathway. We found that PIP5Kα, an isoform of PIP5K, interacts with Nedd4-1, a HECT domain-containing ubiquitin E3 ligase, and undergoes proteasomal degradation via Nedd4-1-mediated polyubiquitination at lysine 88, which leads to reduction in PIP2 levels. Furthermore, we found that the mutation K88R enhances the inhibition of neurite outgrowth in Neuro2A cells. Our results suggest a functional link of Nedd4 family to modulation of membrane phosphoinositides such as PIP2.

Author dc:creator

• TRAN, HOANG MAI

Contributors dc:contributor

• 이, 상윤
• 대학원 의생명과학과
• 201325294

• PIP5Kα
• Nedd4-1
• PIP2
• degradation
• ubiquitination
• neurite outgrowth

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000021983
000000021983

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/13018