DOI: 10.1073/pnas.032404099. Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes

Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes

10.1073/pnas.032404099

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Phosphorylation of proteins on serine/threonine residues preceding proline is a key signaling mechanism. The conformation and function of a subset of these phosphorylated proteins is regulated by the prolyl isomerase Pin1 through isomerization of phosphorylated Ser/Thr-Pro bonds. Although young Pin1 −/− mice have been previously shown to develop normally, we show here that they displayed a range of cell-proliferative abnormalities, including decreased body weight and testicular and retinal atrophies. Furthermore, in Pin1 −/− adult females, the breast epithelial compartment failed to undergo the massive proliferative changes associated with pregnancy. Interestingly, many of these Pin1-deficient phenotypes such as retinal hypoplasia and mammary gland impairment are also the characteristic of cyclin D1-deficient mice. Cyclin D1 levels were significantly reduced in many tissues in Pin1-deficient mice, including retina and breast epithelial cells from pregnant mice. Moreover, Pin1 directly bound to cyclin D1 phosphorylated on Thr-286–Pro increased cyclin D1 in the nucleus and stabilized cyclin D1. These results indicate that Pin1 positively regulates cyclin D1 function at the transcriptional level, as demonstrated previously, and also through posttranslational stabilization, which together explain why Pin1 loss-of-function phenotypes in the mouse resemble cyclin D1-null phenotypes. Our results provide genetic evidence for an essential role of Pin1 in maintaining cell proliferation and regulating cyclin D1 function.

Bibliography

Liou, Y.-C., Ryo, A., Huang, H.-K., Lu, P.-J., Bronson, R., Fujimori, F., Uchida, T., Hunter, T., & Lu, K. P. (2002). Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes. Proceedings of the National Academy of Sciences, 99(3), 1335â1340.

Authors 9

Yih-Cherng Liou (first)
Akihide Ryo (additional)
Han-Kuei Huang (additional)
Pei-Jung Lu (additional)
Roderick Bronson (additional)
Fumihiro Fujimori (additional)
Takafumi Uchida (additional)
Tony Hunter (additional)
Kun Ping Lu (additional)

References 41 Referenced 278

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:36 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 9:05 a.m.)
Indexed	1 month, 2 weeks ago (July 16, 2025, 9:11 a.m.)
Issued	23 years, 7 months ago (Jan. 22, 2002)
Published	23 years, 7 months ago (Jan. 22, 2002)
Published Online	23 years, 7 months ago (Jan. 22, 2002)
Published Print	23 years, 6 months ago (Feb. 5, 2002)

Funders 0

None

BibTeX

@article{Liou_2002, title={Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.032404099}, DOI={10.1073/pnas.032404099}, number={3}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Liou, Yih-Cherng and Ryo, Akihide and Huang, Han-Kuei and Lu, Pei-Jung and Bronson, Roderick and Fujimori, Fumihiro and Uchida, Takafumi and Hunter, Tony and Lu, Kun Ping}, year={2002}, month=jan, pages={1335–1340} }

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