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p21 cip1 is required for the differentiation of oligodendrocytes independently of cell cycle withdrawal
Author(s) -
Zezula Jürgen,
CasacciaBonnefil Patrizia,
Ezhevsky Sergei A,
Osterhout Donna J,
Levine Joel M,
Dowdy Steve F,
Chao Moses V,
Koff Andrew
Publication year - 2001
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kve008
Subject(s) - microbiology and biotechnology , cell cycle , cellular differentiation , cell cycle checkpoint , oligodendrocyte , biology , cell cycle protein , cyclin dependent kinase , cell , neuroscience , genetics , myelin , gene , central nervous system
Differentiation of most cell types requires both establishment of G 1 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–p16 Ink4a protein. We concluded that the two cdk inhibitors serve non‐redundant 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.