CIP2A Inhibits PP2A in Human Malignancies

Melissa R. Junttila; Pietri Puustinen; Minna Niemelä; Raija Ahola; Hugh Arnold; Trine Böttzauw; Risto Ala-aho; Christina Nielsen; Johanna Ivaska; Yoichi Taya; Shi-Long Lu; Shujun Lin; Edward K.L. Chan; Xiao-Jing Wang; Reidar Grènman; Jürgen Kast; Tuula Kallunki; Rosalie Sears; Veli-Matti Kähäri; Jukka Westermarck

doi:10.1016/j.cell.2007.04.044

CIP2A Inhibits PP2A in Human Malignancies

Melissa R. Junttila
, Pietri Puustinen
, Minna Niemelä
, Raija Ahola
, Hugh Arnold
, Trine Böttzauw
, Risto Ala-aho
, Christina Nielsen
, Johanna Ivaska
, Yoichi Taya
, Shi-Long Lu
, Shujun Lin
, Edward K.L. Chan
, Xiao-Jing Wang
, Reidar Grènman
, Jürgen Kast
, Tuula Kallunki
, Rosalie Sears
, Veli-Matti Kähäri
, Jukka Westermarck^*

^*Corresponding author for this work

VTT Technical Research Centre of Finland

Oregon Health and Science University
Danish Cancer Society
National Cancer Center Research Institute
Shenyang University
University of British Columbia
University of Florida
Turku University Hospital
Tampere University
Tampere University Hospital (TAYS)
University of Turku
Turku Centre for Biotechnology
Åbo Akademi University
VTT (former employee or external)

Research output: Contribution to journal › Article › Scientific › peer-review

560 Citations (Scopus)

Abstract

Inhibition of protein phosphatase 2A (PP2A) activity has been identified as a prerequisite for the transformation of human cells. However, the molecular mechanisms by which PP2A activity is inhibited in human cancers are currently unclear. In this study, we describe a cellular inhibitor of PP2A with oncogenic activity. The protein, designated Cancerous Inhibitor of PP2A (CIP2A), interacts directly with the oncogenic transcription factor c-Myc, inhibits PP2A activity toward c-Myc serine 62 (S62), and thereby prevents c-Myc proteolytic degradation. In addition to its function in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation. The oncogenic activity of CIP2A is demonstrated by transformation of human cells by overexpression of CIP2A. Importantly, CIP2A is overexpressed in two common human malignancies, head and neck squamous cell carcinoma (HNSCC) and colon cancer. Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies.

Original language	English
Pages (from-to)	51-62
Journal	Cell
Volume	130
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2007.04.044
Publication status	Published - 2007
MoE publication type	A1 Journal article-refereed

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

HUMDISEASE
SIGNALING

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10.1016/j.cell.2007.04.044

Cite this

Junttila, M. R., Puustinen, P., Niemelä, M., Ahola, R., Arnold, H., Böttzauw, T., Ala-aho, R., Nielsen, C., Ivaska, J., Taya, Y., Lu, S.-L., Lin, S., Chan, E. K. L., Wang, X.-J., Grènman, R., Kast, J., Kallunki, T., Sears, R., Kähäri, V.-M., & Westermarck, J. (2007). CIP2A Inhibits PP2A in Human Malignancies. Cell, 130(1), 51-62. https://doi.org/10.1016/j.cell.2007.04.044

@article{a72e43b0928840e4a7e0c641abce0165,

title = "CIP2A Inhibits PP2A in Human Malignancies",

abstract = "Inhibition of protein phosphatase 2A (PP2A) activity has been identified as a prerequisite for the transformation of human cells. However, the molecular mechanisms by which PP2A activity is inhibited in human cancers are currently unclear. In this study, we describe a cellular inhibitor of PP2A with oncogenic activity. The protein, designated Cancerous Inhibitor of PP2A (CIP2A), interacts directly with the oncogenic transcription factor c-Myc, inhibits PP2A activity toward c-Myc serine 62 (S62), and thereby prevents c-Myc proteolytic degradation. In addition to its function in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation. The oncogenic activity of CIP2A is demonstrated by transformation of human cells by overexpression of CIP2A. Importantly, CIP2A is overexpressed in two common human malignancies, head and neck squamous cell carcinoma (HNSCC) and colon cancer. Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies.",

keywords = "HUMDISEASE, SIGNALING",

author = "Junttila, \{Melissa R.\} and Pietri Puustinen and Minna Niemel{\"a} and Raija Ahola and Hugh Arnold and Trine B{\"o}ttzauw and Risto Ala-aho and Christina Nielsen and Johanna Ivaska and Yoichi Taya and Shi-Long Lu and Shujun Lin and Chan, \{Edward K.L.\} and Xiao-Jing Wang and Reidar Gr{\`e}nman and J{\"u}rgen Kast and Tuula Kallunki and Rosalie Sears and Veli-Matti K{\"a}h{\"a}ri and Jukka Westermarck",

year = "2007",

doi = "10.1016/j.cell.2007.04.044",

language = "English",

volume = "130",

pages = "51--62",

journal = "Cell",

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TY - JOUR

T1 - CIP2A Inhibits PP2A in Human Malignancies

AU - Junttila, Melissa R.

AU - Puustinen, Pietri

AU - Niemelä, Minna

AU - Ahola, Raija

AU - Arnold, Hugh

AU - Böttzauw, Trine

AU - Ala-aho, Risto

AU - Nielsen, Christina

AU - Ivaska, Johanna

AU - Taya, Yoichi

AU - Lu, Shi-Long

AU - Lin, Shujun

AU - Chan, Edward K.L.

AU - Wang, Xiao-Jing

AU - Grènman, Reidar

AU - Kast, Jürgen

AU - Kallunki, Tuula

AU - Sears, Rosalie

AU - Kähäri, Veli-Matti

AU - Westermarck, Jukka

PY - 2007

Y1 - 2007

N2 - Inhibition of protein phosphatase 2A (PP2A) activity has been identified as a prerequisite for the transformation of human cells. However, the molecular mechanisms by which PP2A activity is inhibited in human cancers are currently unclear. In this study, we describe a cellular inhibitor of PP2A with oncogenic activity. The protein, designated Cancerous Inhibitor of PP2A (CIP2A), interacts directly with the oncogenic transcription factor c-Myc, inhibits PP2A activity toward c-Myc serine 62 (S62), and thereby prevents c-Myc proteolytic degradation. In addition to its function in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation. The oncogenic activity of CIP2A is demonstrated by transformation of human cells by overexpression of CIP2A. Importantly, CIP2A is overexpressed in two common human malignancies, head and neck squamous cell carcinoma (HNSCC) and colon cancer. Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies.

AB - Inhibition of protein phosphatase 2A (PP2A) activity has been identified as a prerequisite for the transformation of human cells. However, the molecular mechanisms by which PP2A activity is inhibited in human cancers are currently unclear. In this study, we describe a cellular inhibitor of PP2A with oncogenic activity. The protein, designated Cancerous Inhibitor of PP2A (CIP2A), interacts directly with the oncogenic transcription factor c-Myc, inhibits PP2A activity toward c-Myc serine 62 (S62), and thereby prevents c-Myc proteolytic degradation. In addition to its function in c-Myc stabilization, CIP2A promotes anchorage-independent cell growth and in vivo tumor formation. The oncogenic activity of CIP2A is demonstrated by transformation of human cells by overexpression of CIP2A. Importantly, CIP2A is overexpressed in two common human malignancies, head and neck squamous cell carcinoma (HNSCC) and colon cancer. Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies.

KW - HUMDISEASE

KW - SIGNALING

U2 - 10.1016/j.cell.2007.04.044

DO - 10.1016/j.cell.2007.04.044

M3 - Article

SN - 0092-8674

VL - 130

SP - 51

EP - 62

JO - Cell

JF - Cell

IS - 1

ER -

CIP2A Inhibits PP2A in Human Malignancies

Abstract

UN SDGs

Keywords

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