PPP2R1B

This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes a beta isoform of the constant regulatory subunit A. Defects in this gene could be the cause of some lung and colon cancers. At least two transcript variants encoding different isoforms have been found for this gene.

The PPP2R1B gene was discovered as part of the Human Genome Project research center focused on chromosome 11.{{cite journal | vauthors = Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, Evans GA | title = Alterations of the PPP2R1B gene in human lung and colon cancer | journal = Science | volume = 282 | issue = 5387 | pages = 284–287 | date = October 1998 | pmid = 9765152 | doi = 10.1126/science.282.5387.284 }}{{cite patent | country = US | number = 6743906 | title = PPP2R1B is a tumor suppressor | url = https://patents.google.com/patent/US6743906B1/ | gdate = 1 June 2004 | assign = University of Texas System | inventor = Evans GA, Wang SS, Esplin ED, Li JL, Huang L }}

Somatic alterations in PPP2R1B have been identified in colorectal and lung cancer tumors and cell lines, with evidence that these alterations affect protein function, supporting a role for PPP2R1B as a candidate tumor suppressor gene in these cancers. Experimental studies have shown that suppression of PPP2R1B expression enables immortalized human cells to become tumorigenic, and that the wild-type protein forms a complex with the small GTPase RalA. These findings support the role of PPP2R1B as a tumor suppressor involved in regulating RalA function.{{cite journal | vauthors = Sablina AA, Chen W, Arroyo JD, Corral L, Hector M, Bulmer SE, DeCaprio JA, Hahn WC | title = The tumor suppressor PP2A Abeta regulates the RalA GTPase | journal = Cell | volume = 129 | issue = 5 | pages = 969–982 | date = June 2007 | pmid = 17540176 | pmc = 1945132 | doi = 10.1016/j.cell.2007.03.047 }}

A case series described nine cancer patients with germline loss-of-function (LOF) variants in PPP2R1B, with breast cancer being the most frequently observed diagnosis.{{cite journal | vauthors = Mazhar S, O'Connor CM, Harold A, Dowdican AC, Ulintz PJ, Hanson EN, Zhang Y, Jacobs MF, Merajver SD, Jackson MW, Scott A, Sieuwerts AM, Chinnaiyan AM, Narla G | title = Germline loss-of-function mutations in PPP2R1B in patients with a personal and family history of cancer | journal = JCI Insight | pages = e186288 | date = April 2025 | pmid = 40178903 | doi = 10.1172/jci.insight.186288 | doi-access = free }} In all documented cases, individuals also had a family history of cancers including breast, ovarian, prostate, uterine, renal, and colorectal cancer, suggesting that PPP2R1B may function as a predisposition gene in breast and potentially other cancers.

PPP2R1B has been shown to interact with:

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• PPP2CA,
• PPP2CB,
• PPP2R2A,{{cite journal | vauthors = Kamibayashi C, Lickteig RL, Estes R, Walter G, Mumby MC | title = Expression of the A subunit of protein phosphatase 2A and characterization of its interactions with the catalytic and regulatory subunits | journal = The Journal of Biological Chemistry | volume = 267 | issue = 30 | pages = 21864–21872 | date = October 1992 | pmid = 1328247 | doi = 10.1016/S0021-9258(19)36692-X | doi-access = free }}
• PPP2R3B,{{cite journal | vauthors = Zhou J, Pham HT, Ruediger R, Walter G | title = Characterization of the Aalpha and Abeta subunit isoforms of protein phosphatase 2A: differences in expression, subunit interaction, and evolution | journal = The Biochemical Journal | volume = 369 | issue = Pt 2 | pages = 387–398 | date = January 2003 | pmid = 12370081 | pmc = 1223084 | doi = 10.1042/BJ20021244 }}
• PPP2R5A,{{cite journal | vauthors = Goudreault M, D'Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, Chaudhry S, Chen GI, Sicheri F, Nesvizhskii AI, Aebersold R, Raught B, Gingras AC | title = A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein | journal = Molecular & Cellular Proteomics | volume = 8 | issue = 1 | pages = 157–171 | date = January 2009 | pmid = 18782753 | pmc = 2621004 | doi = 10.1074/mcp.M800266-MCP200 | doi-access = free }}
• PPP2R5B,
• PPP2R5C,
• PPP2R5D, and
• PPP2R5E.{{cite journal | vauthors = McCright B, Rivers AM, Audlin S, Virshup DM | title = The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm | journal = The Journal of Biological Chemistry | volume = 271 | issue = 36 | pages = 22081–22089 | date = September 1996 | pmid = 8703017 | doi = 10.1074/jbc.271.36.22081 | doi-access = free }}

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{{Reflist}}

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• {{cite journal | vauthors = Zolnierowicz S | title = Type 2A protein phosphatase, the complex regulator of numerous signaling pathways | journal = Biochemical Pharmacology | volume = 60 | issue = 8 | pages = 1225–1235 | date = October 2000 | pmid = 11007961 | doi = 10.1016/S0006-2952(00)00424-X }}
• {{cite journal | vauthors = Kamibayashi C, Lickteig RL, Estes R, Walter G, Mumby MC | title = Expression of the A subunit of protein phosphatase 2A and characterization of its interactions with the catalytic and regulatory subunits | journal = The Journal of Biological Chemistry | volume = 267 | issue = 30 | pages = 21864–21872 | date = October 1992 | pmid = 1328247 | doi = 10.1016/S0021-9258(19)36692-X | doi-access = free }}
• {{cite journal | vauthors = Tung HY, De Rocquigny H, Zhao LJ, Cayla X, Roques BP, Ozon R | title = Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr | journal = FEBS Letters | volume = 401 | issue = 2-3 | pages = 197–201 | date = January 1997 | pmid = 9013886 | doi = 10.1016/S0014-5793(96)01470-6 | s2cid = 23293768 | doi-access = free | bibcode = 1997FEBSL.401..197T }}
• {{cite journal | vauthors = Adler HT, Nallaseth FS, Walter G, Tkachuk DC | title = HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A | journal = The Journal of Biological Chemistry | volume = 272 | issue = 45 | pages = 28407–28414 | date = November 1997 | pmid = 9353299 | doi = 10.1074/jbc.272.45.28407 | doi-access = free }}
• {{cite journal | vauthors = Ruediger R, Brewis N, Ohst K, Walter G | title = Increasing the ratio of PP2A core enzyme to holoenzyme inhibits Tat-stimulated HIV-1 transcription and virus production | journal = Virology | volume = 238 | issue = 2 | pages = 432–443 | date = November 1997 | pmid = 9400615 | doi = 10.1006/viro.1997.8873 | doi-access = free }}
• {{cite journal | vauthors = Wang SS, Esplin ED, Li JL, Huang L, Gazdar A, Minna J, Evans GA | title = Alterations of the PPP2R1B gene in human lung and colon cancer | journal = Science | volume = 282 | issue = 5387 | pages = 284–287 | date = October 1998 | pmid = 9765152 | doi = 10.1126/science.282.5387.284 | bibcode = 1998Sci...282..284W }}
• {{cite journal | vauthors = Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y | title = Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus | journal = The Journal of Biological Chemistry | volume = 274 | issue = 24 | pages = 17267–17274 | date = June 1999 | pmid = 10358086 | doi = 10.1074/jbc.274.24.17267 | doi-access = free }}
• {{cite journal | vauthors = Campbell IG, Manolitsas T | title = Absence of PPP2R1B gene alterations in primary ovarian cancers | journal = Oncogene | volume = 18 | issue = 46 | pages = 6367–6369 | date = November 1999 | pmid = 10597236 | doi = 10.1038/sj.onc.1203070 | doi-access = free }}
• {{cite journal | vauthors = Takagi Y, Futamura M, Yamaguchi K, Aoki S, Takahashi T, Saji S | title = Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers | journal = Gut | volume = 47 | issue = 2 | pages = 268–271 | date = August 2000 | pmid = 10896920 | pmc = 1727986 | doi = 10.1136/gut.47.2.268 }}
• {{cite journal | vauthors = Baysal BE, Willett-Brozick JE, Taschner PE, Dauwerse JG, Devilee P, Devlin B | title = A high-resolution integrated map spanning the SDHD gene at 11q23: a 1.1-Mb BAC contig, a partial transcript map and 15 new repeat polymorphisms in a tumour-suppressor region | journal = European Journal of Human Genetics | volume = 9 | issue = 2 | pages = 121–129 | date = February 2001 | pmid = 11313745 | doi = 10.1038/sj.ejhg.5200585 | doi-access = free }}
• {{cite journal | vauthors = Ruediger R, Pham HT, Walter G | title = Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the A beta subunit gene | journal = Oncogene | volume = 20 | issue = 15 | pages = 1892–1899 | date = April 2001 | pmid = 11313937 | doi = 10.1038/sj.onc.1204279 | doi-access = free }}
• {{cite journal | vauthors = Yokoyama N, Reich NC, Miller WT | title = Involvement of protein phosphatase 2A in the interleukin-3-stimulated Jak2-Stat5 signaling pathway | journal = Journal of Interferon & Cytokine Research | volume = 21 | issue = 6 | pages = 369–378 | date = June 2001 | pmid = 11440634 | doi = 10.1089/107999001750277844 }}
• {{cite journal | vauthors = Elder RT, Yu M, Chen M, Zhu X, Yanagida M, Zhao Y | title = HIV-1 Vpr induces cell cycle G2 arrest in fission yeast (Schizosaccharomyces pombe) through a pathway involving regulatory and catalytic subunits of PP2A and acting on both Wee1 and Cdc25 | journal = Virology | volume = 287 | issue = 2 | pages = 359–370 | date = September 2001 | pmid = 11531413 | doi = 10.1006/viro.2001.1007 | doi-access = free }}
• {{cite journal | vauthors = Yang J, Fan GH, Wadzinski BE, Sakurai H, Richmond A | title = Protein phosphatase 2A interacts with and directly dephosphorylates RelA | journal = The Journal of Biological Chemistry | volume = 276 | issue = 51 | pages = 47828–47833 | date = December 2001 | pmid = 11591705 | pmc = 2665282 | doi = 10.1074/jbc.M106103200 | doi-access = free }}
• {{cite journal | vauthors = Strack S, Ruediger R, Walter G, Dagda RK, Barwacz CA, Cribbs JT | title = Protein phosphatase 2A holoenzyme assembly: identification of contacts between B-family regulatory and scaffolding A subunits | journal = The Journal of Biological Chemistry | volume = 277 | issue = 23 | pages = 20750–20755 | date = June 2002 | pmid = 11929880 | doi = 10.1074/jbc.M202992200 | doi-access = free }}
• {{cite journal | vauthors = Hemmer S, Wasenius VM, Haglund C, Zhu Y, Knuutila S, Franssila K, Joensuu H | title = Alterations in the suppressor gene PPP2R1B in parathyroid hyperplasias and adenomas | journal = Cancer Genetics and Cytogenetics | volume = 134 | issue = 1 | pages = 13–17 | date = April 2002 | pmid = 11996789 | doi = 10.1016/S0165-4608(01)00597-0 }}

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