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ID 117150
Title Alternative
内因性PP2A阻害因CIP2Aの過剰な発現は骨髄腫細胞の増殖・生存に極めて重要である
CIP2A-PP2A in myeloma
Author
Oda, Asuka Tokushima University
Seki, Aiko Okayama University
Inoue, Yusuke Tokushima University
Tanimoto, Kotaro Tokushima University
Higa, Yoshiki Tokushima University
Maruhashi, Tomoko Tokushima University
Yamagami, Hiroki Tokushima University
Sawa, Yoshihiko Okayama University
Keywords
multiple myeloma
TAK1
CIP2A
PP2A
Content Type
Thesis or Dissertation
Description
The serine/threonine kinase TAK1 is constitutively overexpressed and auto-phosphorylated in multiple myeloma (MM) cells. Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase which dephosphorylates proteins phosphorylated by various serine/threonine kinases to regulate multiple cellular functions. We recently reported that the serine/threonine kinase TGF-β-activated kinase-1 (TAK1) is highly expressed and auto-phosphorylated to mediate critical growth and survival signaling in MM cells. We demonstrate here that regulation of PP2A activity inversely affects the phosphorylation levels of TAK1 in MM cells, and that MM cells aberrantly overexpress cancerous inhibitor of PP2A (CIP2A), an endogenous inhibitor for PP2A. CIP2A gene silencing as well as treatment with the CIP2A inhibitor TD52 potently induced MM cell death along with suppression of TAK1 expression in MM cells. These results suggest the critical role of PP2A inactivation via CIP2A upregulation in TAK1 phosphorylation and its protein expression and thereby MM cell growth and survival, posing the CIP2A-PP2A axis as an important therapeutic target.
Journal Title
International Journal of Myeloma
ISSN
21873143
NCID
AA12766965
Publisher
Japanese Society of Myeloma
Volume
12
Issue
2
Start Page
14
End Page
23
Published Date
2022
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者So SHIMIZUの学位論文として提出され,学位審査・授与の対象となっている。
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3640号
Diploma Number
甲口第486号
Granted Date
2022-05-12
Degree Name
Doctor of Dental Science
Grantor
Tokushima University
departments
Oral Sciences
University Hospital
Medical Sciences
Institute of Advanced Medical Sciences