イベント・セミナー
Dynamic phosphorylation of HP1α orchestrates mitotic progression in human cells
講演者：Dr. Supriya G. Prasanth 所属：University of Illinois開催日：2013-09-17 16:30
終了日：2013-09-17 17:30
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講演者 Dr. Supriya G. Prasanth (Associate Professor, University of Illinois)
日時 ９月１７日（火） 午後４時３０分から１時間程度
場所 薬学部第１講義室（１号館５階奥）
演題
Dynamic phosphorylation of HP1α orchestrates mitotic progression in human cells
Arindam Chakraborty, Kannanganattu V. Prasanth and Supriya G. Prasanth
Heterochromatin protein 1α (HP1α), a key player in the establishment and maintenance of higher-order chromatin is implicated in essential cellular processes including transcriptional activation/repression, metaphase chromatid cohesion and centromere organization. Human HP1α is highly phosphorylated; however, the kinase(s) that phosphorylates HP1α and the functional relevance of phosphorylation remained elusive. We demonstrate that HP1α is constitutively phosphorylated within its chromodomain whereas the phosphorylation within the hinge domain occurs preferentially at G2/M phase of the cell cycle. Further, phosphorylation of the hinge region of HP1α by NDR1 kinase is required for mitotic entry and Sgo1 binding to mitotic centromeres. Cells lacking NDR kinase show loss of mitosis-specific phosphorylation of HP1α, persistent association of HP1α with the mitotic chromosome arms and a prometaphase arrest.
Expression of the hinge-specific non-phosphorylatable-HP1α mutant phenocopies the mitotic abnormalities of NDR-depleted cells.
NDR-depleted cells expressing hinge-specific phosphomimetic HP1α mutant rescued the prometaphase entry defects, but arrested the cells at telophase with abnormal daughter nuclei, suggesting that the dephosphorylation of HP1α within the hinge domain is essential for mitotic exit. We demonstrate that the phosphorylation-dephosphorylation cycle of HP1α is essential for accurate mitotic progression.
代表論文
Dynamic association of ORCA with prereplicative complex components regulates DNA replication initiation.
Shen Z, Chakraborty A, Jain A, Giri S, Ha T, Prasanth KV, Prasanth SG.
Mol Cell Biol. 2012 Aug;32(15):3107-20. doi: 10.1128/MCB.00362-12. Epub
2012 May 29.
A WD-repeat protein stabilizes ORC binding to chromatin.
Shen Z, Sathyan KM, Geng Y, Zheng R, Chakraborty A, Freeman B, Wang F, Prasanth KV, Prasanth SG.
Mol Cell. 2010 Oct 8;40(1):99-111. doi: 10.1016/j.molcel.2010.09.021.
Human origin recognition complex is essential for HP1 binding to chromatin and heterochromatin organization.
Prasanth SG, Shen Z, Prasanth KV, Stillman B.
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15093-8. doi:
10.1073/pnas.1009945107
世話人
片山 勉・川上広宣
（薬学研究院・分子生物薬学分野 内6641）