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)

Research output: Contribution to journalArticleScientificpeer-review

405 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 languageEnglish
Pages (from-to)51-62
JournalCell
Volume130
Issue number1
DOIs
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed

Fingerprint

Protein Phosphatase 2
Neoplasms
Cells
Proto-Oncogene Proteins c-myc
Squamous Cell Neoplasms
Oncogene Proteins
Cell growth
Head and Neck Neoplasms
Colonic Neoplasms
Serine
Tumors
Transcription Factors
Stabilization
Degradation
Growth
Proteins

Keywords

  • HUMDISEASE
  • SIGNALING

Cite this

Junttila, M. R., Puustinen, P., Niemelä, M., Ahola, R., Arnold, H., Böttzauw, T., ... Westermarck, J. (2007). CIP2A Inhibits PP2A in Human Malignancies. Cell, 130(1), 51-62. https://doi.org/10.1016/j.cell.2007.04.044
Junttila, Melissa R. ; Puustinen, Pietri ; Niemelä, Minna ; Ahola, Raija ; Arnold, Hugh ; Böttzauw, Trine ; Ala-aho, Risto ; Nielsen, Christina ; Ivaska, Johanna ; Taya, Yoichi ; Lu, Shi-Long ; Lin, Shujun ; Chan, Edward K.L. ; Wang, Xiao-Jing ; Grènman, Reidar ; Kast, Jürgen ; Kallunki, Tuula ; Sears, Rosalie ; Kähäri, Veli-Matti ; Westermarck, Jukka. / CIP2A Inhibits PP2A in Human Malignancies. In: Cell. 2007 ; Vol. 130, No. 1. pp. 51-62.
@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",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",

}

Junttila, MR, 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, EKL, Wang, X-J, Grènman, R, Kast, J, Kallunki, T, Sears, R, Kähäri, V-M & Westermarck, J 2007, 'CIP2A Inhibits PP2A in Human Malignancies', Cell, vol. 130, no. 1, pp. 51-62. https://doi.org/10.1016/j.cell.2007.04.044

CIP2A Inhibits PP2A in Human Malignancies. / Junttila, Melissa R.; Puustinen, Pietri; Niemelä, Minna; Ahola, Raija; Arnold, Hugh; Böttzauw, Trine; Ala-aho, Risto; Nielsen, Christina; Ivaska, Johanna; Taya, Yoichi; Lu, Shi-Long; Lin, Shujun; Chan, Edward K.L.; Wang, Xiao-Jing; Grènman, Reidar; Kast, Jürgen; Kallunki, Tuula; Sears, Rosalie; Kähäri, Veli-Matti; Westermarck, Jukka (Corresponding Author).

In: Cell, Vol. 130, No. 1, 2007, p. 51-62.

Research output: Contribution to journalArticleScientificpeer-review

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

VL - 130

SP - 51

EP - 62

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1

ER -

Junttila MR, Puustinen P, Niemelä M, Ahola R, Arnold H, Böttzauw T et al. CIP2A Inhibits PP2A in Human Malignancies. Cell. 2007;130(1):51-62. https://doi.org/10.1016/j.cell.2007.04.044