p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors.

p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Research Abstract Details 

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p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Abstract Text:

Feng Bai,Xin-Hai Pei,Toru Nishikawa,Matthew D Smith,Yue Xiong,

Mutant mice lacking both cyclin-dependent kinase (CDK) inhibitors p18(Ink4c) and p27(Kip1) develop a tumor spectrum reminiscent of human multiple endocrine neoplasia (MEN) syndromes. To determine how p18 and p27 genetically interact with Men1, the tumor suppressor gene mutated in familial MEN1, we characterized p18-Men1 and p27-Men1 double mutant mice. Compared with their corresponding single mutant littermates, the p18(-/-); Men1(+/-) mice develop tumors at an accelerated rate and with an increased incidence in the pituitary, thyroid, parathyroid, and pancreas. In the pituitary and pancreatic islets, phosphorylation of the retinoblastoma (Rb) protein at both CDK2 and CDK4/6 sites was increased in p18(-/-) and Men1(+/-) cells and was further increased in p18(-/-); Men1(+/-) cells. The remaining wild-type Men1 allele was lost in most tumors from Men1(+/-) mice but was retained in most tumors from p18(-/-); Men1(+/-) mice. Combined mutations of p27(-/-) and Men1(+/-), in contrast, did not exhibit noticeable synergistic stimulation of Rb kinase activity, cell proliferation, and tumor growth. These results demonstrate that functional collaboration exists between p18 and Men1 and suggest that Men1 may regulate additional factor(s) that interact with p18 and p27 differently.

p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Publishing Authors By Initials

F Bai,XH Pei,T Nishikawa,MD Smith,Y Xiong,

For similar proteins: dna-binding proteins: retinoblastoma protein research abstracts see: proteins: dna-binding proteins: retinoblastoma protein research

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p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Molecular and cellular biology

VOLUME: 27

Page Numbers: 1495-504

Journal Abbreviation: Mol. Cell. Biol.

ISSN: 0270-7306

DAY: 4

MONTH: 12

YEAR: 2006

p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8109087

p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Keywords Mesh Terms:

KEYWORDS: Retinoblastoma Protein

MESH TERMS: metabolism

Chemical & Substance for Abstract: p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Information

Substance Name: Cyclin-Dependent Kinases

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors.

AFFILIATION: Lineberger Comprehensive Cancer Center, Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA 68377

ACRONYM: CA

MEDLINETA: Mol Cell Biol

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