Constitutively active-RSK2 induces chromosomal instability through diverse mechanisms

The Ras/mitogen-activated protein kinase (MAPK) signaling pathway regulates various cellular processes including cell survival, cell proliferation cell motility and cell cycle regulation. And mutation or activation of the signaling pathway has been related to cancer development. Cancer cell has a state in which the number of chromosomes in a cell deviates from multiples of the haploid number of chromosomes (aneuploidy). The accumulation of chromosome imbalances generated by the sequential loss and/or gain of single chromosomes through chromosomal instability may be the most common pathway to aneuploidy. We observed that constitutively acvtive RSK2 induced chromosomal instability such as lagging chromosome and chromosome bridge, micro-nucleus and abnormal number of chromosome. Mechanism study revealed that constitutively active RSK2 induced chromosomal instability through spindle assembly checkpoint defects and kinetochore-microtubule (KT-MT) attachment defects. Since RSK2 localizes in microtubule during mitosis, we focused on the relationship between RSK2 and microtubule. We nalyzed kinetochore-microtubule (KT-MT) attachment dynamics through cold stable assay and nocodazole sensitivity assay. Interestingly, these results indicate that constitutively active RSK2 enhanced the stability of microtubules. In addition, we observed that the co-transfection of RSK2 and MCAK decreased lagging chromosome and chromosome bridge during anaphase, indicating that enhancement of kinetochore microtubule stability was indeed the cause of CIN in these cells. Taken together, constitutively active RSK2 induced chromosomal instability through increase in the stability of microtubules. Yet unidentified effect of RSK2 activation in SAC activity also seems to affect CIN. We hereby provide a possible new insight on therole of RSK2 activation in cancer formation as well as to cancer progression.

Author dc:creator

• 박, 채린

Contributors dc:contributor

• 이, 재호
• 대학원 의생명과학과
• 200924419

• RSK2
• chromosomal instability (CIN)
• microtubule

Language dc:language

ko

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000014714
000000014714

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/8594