♠ 주제 : Targeting mortalin in MEK/ERK-dependent tumors 
♠ 연사 : 박종인교수님 (Medical College of Wisconsin)        
♠ 일시 : 2021년 11월 02일 17:00~18:00  
♠ 초청 : 최상돈교수님(내선 2600)  

 Abstract 

Mortalin [also known as heat shock protein family A (Hsp70) member 9 (HSPA9) or glucose-regulated protein 75 (GRP75)] is a mitochondrial molecular chaperone that is often upregulated and mislocalized in tumors with abnormal activation of the kinases MEK1/2 and ERK1/2.  We found that mortalin depletion was lethal to immortalized normal cells expressing K-RasG12V or B-RafV600E , but not wild type K-Ras or B-Raf, and that MEK-ERK–sensitive regulation of the client-binding domain in mortalin was critical to life/death decisions in these cells. Proteomics screening identified adenine nucleotide translocase 3 (ANT3) as a previously unknown mortalin client and life/death effector.  Mechanistically, increased MEK-ERK signaling activity and mortalin function converge in opposition on the regulation of mitochondrial permeability. Specifically, whereas MEK-ERK activity increased mitochondrial permeability by promoting the interaction between ANT3 and the peptidyl-prolyl isomerase cyclophilin D (CypD), mortalin decreased mitochondrial permeability by inhibiting this interaction.  As such, mortalin depletion increased mitochondrial permeability in MEK-ERK–deregulated cells, to the level triggering cell death.  Moreover, chemical inhibitors of mortalin effectively suppressed the proliferation of K-RasG12V or B-RafV600E mutant tumor cells in vitro and in vivo, including B-Raf inhibitor-resistant B-RafV600E melanoma cells. This specific relationship between mortalin and deregulated MEK-ERK pathway activity suggest that mortalin has potential as a selective therapeutic target. 

♠줌링크 

Topic: MST6016_ 분자과학기술세미나Ⅱ(O1413-1) [박종인교수님] 
Time: Nov 2, 2021 05:00 PM Seoul 

https://ajou-ac-kr.zoom.us/j/89959570105?

pwd=cy85YUk0eG5NU1pLZGo0SlVxV3RhUT09 
Meeting ID: 899 5957 0105 Passcode: 070338