P21cip1 is required for the differentiation of oligodendrocytes independently of cell cycle withdrawal Journal Article
| Authors: | Zezula, J.; Casaccia-Bonnefil, P.; Ezhevsky, S. A.; Osterhout, D. J.; Levine, J. M.; Dowdy, S. F.; Chao, M. V.; Koff, A. |
| Article Title: | P21cip1 is required for the differentiation of oligodendrocytes independently of cell cycle withdrawal |
| Abstract: | Differentiation of most cell types requires both establishment of G1 arrest and the induction of a program related to achieving quiescence. We have chosen to study the differentiation of oligodendrocyte cells to determine the role of p27 and p21 in this process. Here we report that both p27 and p21 are required for the appropriate differentiation of these cells. p27 is required for proper withdrawal from the cell cycle, p21 is not. Instead, p21 is required for the establishment of the differentiation program following growth arrest. Similar observations were made in vivo. We show that p21-/- cells withdraw from the cell cycle similar to wild-type cells; however, early in animal life, the brain is hypomyelinated, inferring that the loss of p21 delayed myelination in the cerebellum. We found that we could complement or bypass the differentiation failure in p21-/- cells with either PD98059, an inhibitor of Mek1, or by transducing them with a tat-p16Ink4a protein. We concluded that the two cdk inhibitors serve nonredundant roles in this program of differentiation, with p27 being responsible for arrest and p21 having a function in differentiation independent of its ability to control exit from the cell cycle. |
| Keywords: | immunohistochemistry; controlled study; unclassified drug; nonhuman; cell cycle protein; animal cell; mouse; animal; metabolism; animals; cell cycle proteins; mice; animal tissue; cerebellum; cells, cultured; cell cycle; cell division; protein p16; mitogen activated protein kinase kinase 1; genotype; in vivo study; cell differentiation; drug effect; enzyme inhibitor; protein serine threonine kinase; physiology; time; time factors; cell type; genetic transduction; animalia; transduction, genetic; drug antagonism; kinetics; cell culture; brain; enzyme inhibitors; protein-serine-threonine kinases; cyclin dependent kinase inhibitor 1b; transactivator protein; protein p27; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; newborn; binding protein; flavonoid; flavonoids; cdkn1a protein, mouse; cyclin dependent kinase inhibitor 1a; cyclin-dependent kinase inhibitor p16; cyclin-dependent kinase inhibitor p21; animals, newborn; cycline; tumor suppressor protein; cyclins; cyclin dependent kinase inhibitor; roscovitine; protein p21; mitogen activated protein kinase kinase; mitogen-activated protein kinase kinases; cell cycle g1 phase; map kinase kinase 1; antimetabolite; myelination; broxuridine; bromodeoxyuridine; life; cdkn1b protein, mouse; oligodendroglia; microtubule-associated proteins; microtubule associated protein; mitosis inhibition; antimetabolites; 2 (2 amino 3 methoxyphenyl)chromone; protein p16ink4a; map2k1 protein, mouse; priority journal; article |
| Journal Title: | EMBO Reports |
| Volume: | 2 |
| Issue: | 1 |
| ISSN: | 1469-221X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2001-01-15 |
| Start Page: | 27 |
| End Page: | 34 |
| Language: | English |
| DOI: | 10.1093/embo-reports/kve008 |
| PUBMED: | 11252720 |
| PROVIDER: | scopus |
| PMCID: | PMC1083805 |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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