Literature DB >> 26507691

All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase.

Jaya Sangodkar1, Caroline C Farrington2, Kimberly McClinch3, Matthew D Galsky3, David B Kastrinsky4, Goutham Narla2.   

Abstract

Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase involved in the regulation of many cellular processes. A confirmed tumor suppressor protein, PP2A is genetically altered or functionally inactivated in many cancers highlighting a need for its therapeutic reactivation. In this review we discuss recent literature on PP2A: the elucidation of its structure and the functions of its subunits, and the identification of molecular lesions and post-translational modifications leading to its dysregulation in cancer. A final section will discuss the proteins and small molecules that modulate PP2A and how these might be used to target dysregulated forms of PP2A to treat cancers and other diseases.
© 2015 FEBS.

Entities:  

Keywords:  CIP2A; PP2A; SET; cancer; cancer biology; cell signaling; drug development; protein phosphatases; structural biology; tumor suppressors

Mesh:

Substances:

Year:  2015        PMID: 26507691      PMCID: PMC4803620          DOI: 10.1111/febs.13573

Source DB:  PubMed          Journal:  FEBS J        ISSN: 1742-464X            Impact factor:   5.542


  208 in total

1.  A truncated isoform of the PP2A B56 subunit promotes cell motility through paxillin phosphorylation.

Authors:  A Ito; T R Kataoka; M Watanabe; K Nishiyama; Y Mazaki; H Sabe; Y Kitamura; H Nojima
Journal:  EMBO J       Date:  2000-02-15       Impact factor: 11.598

Review 2.  Involvement of PP2A in viral and cellular transformation.

Authors:  Jason D Arroyo; William C Hahn
Journal:  Oncogene       Date:  2005-11-21       Impact factor: 9.867

3.  Induction of cancer cell apoptosis by alpha-tocopheryl succinate: molecular pathways and structural requirements.

Authors:  J Neuzil; T Weber; A Schröder; M Lu; G Ostermann; N Gellert; G C Mayne; B Olejnicka; A Nègre-Salvayre; M Stícha; R J Coffey; C Weber
Journal:  FASEB J       Date:  2001-02       Impact factor: 5.191

4.  HEAT repeats in the Huntington's disease protein.

Authors:  M A Andrade; P Bork
Journal:  Nat Genet       Date:  1995-10       Impact factor: 38.330

5.  Functional domains of template-activating factor-I as a protein phosphatase 2A inhibitor.

Authors:  S Saito; M Miyaji-Yamaguchi; T Shimoyama; K Nagata
Journal:  Biochem Biophys Res Commun       Date:  1999-06-07       Impact factor: 3.575

6.  Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma.

Authors:  Siân Jones; Tian-Li Wang; Ie-Ming Shih; Tsui-Lien Mao; Kentaro Nakayama; Richard Roden; Ruth Glas; Dennis Slamon; Luis A Diaz; Bert Vogelstein; Kenneth W Kinzler; Victor E Velculescu; Nickolas Papadopoulos
Journal:  Science       Date:  2010-09-08       Impact factor: 47.728

7.  Folate deficiency induces in vitro and mouse brain region-specific downregulation of leucine carboxyl methyltransferase-1 and protein phosphatase 2A B(alpha) subunit expression that correlate with enhanced tau phosphorylation.

Authors:  Jean-Marie Sontag; Viyada Nunbhakdi-Craig; Lisa Montgomery; Erland Arning; Teodoro Bottiglieri; Estelle Sontag
Journal:  J Neurosci       Date:  2008-11-05       Impact factor: 6.167

8.  PP2A activity is controlled by methylation and regulates oncoprotein expression in melanoma cells: a mechanism which participates in growth inhibition induced by chloroethylnitrosourea treatment.

Authors:  Samuel Guénin; Laurent Schwartz; Daniel Morvan; Jean Marc Steyaert; Amandine Poignet; Jean Claude Madelmont; Aicha Demidem
Journal:  Int J Oncol       Date:  2008-01       Impact factor: 5.650

9.  Cornel Iridoid Glycoside Attenuates Tau Hyperphosphorylation by Inhibition of PP2A Demethylation.

Authors:  Cui-Cui Yang; Xue-Xian Kuai; Ya-Li Li; Li Zhang; Jian-Chun Yu; Lin Li; Lan Zhang
Journal:  Evid Based Complement Alternat Med       Date:  2013-12-19       Impact factor: 2.629

10.  Senescence sensitivity of breast cancer cells is defined by positive feedback loop between CIP2A and E2F1.

Authors:  Anni Laine; Harri Sihto; Christophe Come; Mathias T Rosenfeldt; Aleksandra Zwolinska; Minna Niemelä; Anchit Khanna; Edward K Chan; Veli-Matti Kähäri; Pirkko-Liisa Kellokumpu-Lehtinen; Owen J Sansom; Gerard I Evan; Melissa R Junttila; Kevin M Ryan; Jean-Christophe Marine; Heikki Joensuu; Jukka Westermarck
Journal:  Cancer Discov       Date:  2013-01-10       Impact factor: 39.397

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  114 in total

1.  Cortical astroglia undergo transcriptomic dysregulation in the G93A SOD1 ALS mouse model.

Authors:  Sean J Miller; Jenna C Glatzer; Yi-Chun Hsieh; Jeffrey D Rothstein
Journal:  J Neurogenet       Date:  2018-11-06       Impact factor: 1.250

2.  Uncovering BRD4 hyperphosphorylation associated with cellular transformation in NUT midline carcinoma.

Authors:  Ranran Wang; Xing-Jun Cao; Katarzyna Kulej; Wei Liu; Tongcui Ma; Margo MacDonald; Cheng-Ming Chiang; Benjamin A Garcia; Jianxin You
Journal:  Proc Natl Acad Sci U S A       Date:  2017-06-19       Impact factor: 11.205

Review 3.  Targeting PP2A in cancer: Combination therapies.

Authors:  Sahar Mazhar; Sarah E Taylor; Jaya Sangodkar; Goutham Narla
Journal:  Biochim Biophys Acta Mol Cell Res       Date:  2018-09-01       Impact factor: 4.739

Review 4.  APC/C ubiquitin ligase: Functions and mechanisms in tumorigenesis.

Authors:  Morgan S Schrock; Benjamin R Stromberg; Luke Scarberry; Matthew K Summers
Journal:  Semin Cancer Biol       Date:  2020-03-09       Impact factor: 15.707

5.  Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1.

Authors:  Otto Kauko; Susumu Y Imanishi; Evgeny Kulesskiy; Laxman Yetukuri; Teemu Daniel Laajala; Mukund Sharma; Karolina Pavic; Anna Aakula; Christian Rupp; Mikael Jumppanen; Pekka Haapaniemi; Luyao Ruan; Bhagwan Yadav; Veronika Suni; Taru Varila; Garry L Corthals; Jüri Reimand; Krister Wennerberg; Tero Aittokallio; Jukka Westermarck
Journal:  J Biol Chem       Date:  2020-02-18       Impact factor: 5.157

6.  PP2A-B56γ is required for an efficient spindle assembly checkpoint.

Authors:  Prajakta Varadkar; Fatima Abbasi; Kazuyo Takeda; Jade J Dyson; Brent McCright
Journal:  Cell Cycle       Date:  2017-05-31       Impact factor: 4.534

7.  Calcium-binding proteins that are type B″ regulatory subunits of phosphatase 2A in Giardia intestinalis.

Authors:  Magda E Alvarado; Claudia Rubiano; William Sánchez; Andrea Díaz; Moisés Wasserman
Journal:  Parasitol Res       Date:  2018-07-24       Impact factor: 2.289

8.  Sphingolipids inhibit endosomal recycling of nutrient transporters by inactivating ARF6.

Authors:  Brendan T Finicle; Manuel U Ramirez; Gang Liu; Elizabeth M Selwan; Alison N McCracken; Jingwen Yu; Yoosun Joo; Jannett Nguyen; Kevin Ou; Saurabh Ghosh Roy; Victor D Mendoza; Dania Virginia Corrales; Aimee L Edinger
Journal:  J Cell Sci       Date:  2018-06-25       Impact factor: 5.285

Review 9.  The impact of phosphatases on proliferative and survival signaling in cancer.

Authors:  Goutham Narla; Jaya Sangodkar; Christopher B Ryder
Journal:  Cell Mol Life Sci       Date:  2018-05-03       Impact factor: 9.261

10.  Direct activation of PP2A for the treatment of tyrosine kinase inhibitor-resistant lung adenocarcinoma.

Authors:  Rita Tohmé; Sudeh Izadmehr; Sai Gandhe; Giancarlo Tabaro; Sanjay Vallabhaneni; Ava Thomas; Neal Vasireddi; Neil S Dhawan; Avi Ma'ayan; Neelesh Sharma; Matthew D Galsky; Michael Ohlmeyer; Jaya Sangodkar; Goutham Narla
Journal:  JCI Insight       Date:  2019-02-21
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