FAM122A, a new endogenous inhibitor of protein phosphatase 2A

Fan, Li; Liu, Man-Hua; Guo, Meng; Hu, Chuan-Xi; Yan, Zhao-Wen; Chen, Jing; Chen, Guoqiang; Huang, Ying

doi:10.18632/oncotarget.11698

Cited by 30 publications

(41 citation statements)

References 53 publications

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“…Bod1 has also recently been shown to alleviate premature, radiation-induced chromatid separation in human lung and renal cell carcinoma cells, protecting against genomic instability [ 21 ]. Bod1, together with CIP2A [ 22 ], FAM122A [ 23 ], I1PP2A/ANP32A [ 24 ], I2PP2A/SET [ 25 ], TIP [ 26 ] and Arpp-19/Ensa [ 27 , 28 ], forms part of a growing family of PP2A inhibitors that have important roles in supporting cell division. However, little is known about the temporal localization of these PP2A regulators or how they modulate the activity of PP2A towards different substrates.…”

Section: Introductionmentioning

confidence: 99%

The Ndc80 complex targets Bod1 to human mitotic kinetochores

et al. 2017

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Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of protein phosphatase 2A containing the B56 regulatory subunit (PP2A-B56). This phosphatase controls the amount of phosphorylation of several kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis. Like PP2A-B56, Bod1 directly localizes to mitotic kinetochores and is required for correct segregation of mitotic chromosomes. In this report, we have probed the spatio-temporal regulation of Bod1 during mitotic progression. Kinetochore localization of Bod1 increases from nuclear envelope breakdown until metaphase. Phosphorylation of Bod1 at threonine 95 (T95), which increases Bod1's binding to and inhibition of PP2A-B56, peaks in prometaphase when PP2A-B56 localization to kinetochores is highest. We demonstrate here that kinetochore targeting of Bod1 depends on the outer kinetochore protein Ndc80 and not PP2A-B56. Crucially, Bod1 depletion functionally affects Ndc80 phosphorylation at the N-terminal serine 55 (S55), as well as a number of other phosphorylation sites within the outer kinetochore, including Knl1 at serine 24 and 60 (S24, S60), and threonine T943 and T1155 (T943, T1155). Therefore, Ndc80 recruits a phosphatase inhibitor to kinetochores which directly feeds forward to regulate Ndc80, and Knl1 phosphorylation, including sites that mediate the attachment of microtubules to kinetochores.

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Section: Introductionmentioning

confidence: 99%

The Ndc80 complex targets Bod1 to human mitotic kinetochores

et al. 2017

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“…It has 287 amino acids with highly conserved in many species of mammary animals. Previously we reported that FAM122A is an inhibitor of protein phosphatase 2A [5], and more recently, FAM122A has been found to be abnormally upregulated in acute myeloid leukemia (AML) characterized with the dysfunction of myeloid stem cells [6], and is essential for maintaining the growth of AML cells in vitro cultured cells and in vivo AML cell engraftment [7]. In this study, we investigated whether FAM122A has a role in the function of HSCs.…”

Section: To the Editormentioning

confidence: 99%