CIP2A inhibits PP2A in human malignancies

被引：677

作者：

Junttila, Melissa R.

Puustinen, Pietri

Niemela, Minna

Ahola, Raija

Arnold, Hugh

Bottzauw, Trine

Ala-aho, Risto

Nielsen, Christina

Ivaska, Johanna

Taya, Yoichi

Lu, Shi-Long

Lin, Shujun

Chan, Edward K. L.

Wang, Xiao-Jing

Grenman, Reidar

Kast, Juergen

Kallunki, Tuula

Sears, Rosalie

Kahari, Veli-Matti

Westermarck, Jukka ^{[1
]}

机构：

[1] Univ Turku, Ctr Biotechnol, FIN-20520 Turku, Finland

[2] Abo Akad Univ, FIN-20520 Turku, Finland

[3] Univ Turku, Turku Grad Sch Biomed Sci, FIN-20520 Turku, Finland

[4] Univ Turku, Dept Med Biochem & Mol Biol, FIN-20520 Turku, Finland

[5] Univ Turku, Medic Res Lab, FIN-20520 Turku, Finland

[6] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA

[7] Danish Canc Soc, Inst Canc Biol, Apoptosis Lab, DK-2100 Copenhagen, Denmark

[8] VTT Tech Res Ctr Finland, Med Biotechnol, FIN-20520 Turku, Finland

[9] Natl Canc Ctr, Res Inst, Tokyo 1040045, Japan

[10] OHSU, Dept Otolaryngol, Portland, OR 97239 USA

[11] OHSU, Dept Dermatol, Portland, OR 97239 USA

[12] OHSU, Dept Cell & Dev Biol, Portland, OR 97239 USA

[13] Univ British Columbia, Biomed Res Ctr, Vancouver, BC V5Z 1M9, Canada

[14] Univ Florida, Dept Oral Biol, Gainesville, FL 32610 USA

[15] Turku Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, FIN-20520 Turku, Finland

[16] Turku Univ Hosp, Dept Dermatol, FIN-20520 Turku, Finland

[17] Univ Tampere, Inst Med Technol, FIN-33520 Tampere, Finland

[18] Tampere Univ Hosp, FIN-33520 Tampere, Finland

来源：

CELL | 2007年 / 130卷 / 01期

关键词：

D O I：

10.1016/j.cell.2007.04.044

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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 cMyc 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.

引用

页码：51 / 62

页数：12

共 33 条

[1]

Protein phosphatase 2A regulatory subunit b56α associates with c-Myc and negatively regulates c-Myc accumulation [J].