The Cyclin-Dependent Kinase Inhibitor p27Kip1 is a Positive Regulator of Schwann Cell Differentiation In Vitro

被引:14
作者
Li, Honghui [1 ,2 ]
Yang, Huiguang [1 ,2 ]
Liu, Yonghua [1 ,2 ]
Huan, Weipeng [1 ,2 ]
Zhang, Shuangwei [1 ,2 ]
Wu, Gang [1 ,2 ]
Lu, Qiuhui [1 ,2 ]
Wang, Qiuhong [1 ,2 ]
Wang, Youhua [1 ,2 ]
机构
[1] Nantong Univ, Dept Orthopaed, Affiliated Hosp, Nantong 226001, Peoples R China
[2] Nantong Univ, Dept Orthopaed, Coll Med, Nantong 226001, Peoples R China
基金
中国国家自然科学基金;
关键词
p27(Kip1); Schwann cell; Differentiation; Peripheral nerve; CDK INHIBITOR; UBIQUITIN LIGASE; PERIPHERAL-NERVE; MICE LACKING; G(1) PHASE; P27; PROMOTES; PHOSPHORYLATION; MYELINATION; DEGRADATION;
D O I
10.1007/s12031-011-9518-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Schwann cell precursors differentiating into a myelinating phenotype are critical for peripheral nerve development and regeneration. However, little is known about the underlying molecular mechanisms of Schwann cell differentiation. In the present study, we performed a cyclic adenosine monophosphate-induced Schwann cell differentiation model in vitro. Western blot analysis showed that p27(Kip1) expression was upregulated during the differentiation of Schwann cell, while the inhibition of p27(Kip1) expression by short hairpin RNA-mediated knockdown significantly abolished the expression of promyelinating markers and the alteration of cellular morphology. In addition, immunofluorescence revealed a decrease of p27(Kip1) nuclear staining and a concomitant increase of cytoplasmic staining in differentiated Schwann cells. In summary, our data indicated that p27(Kip1) was a positive regulator of Schwann cell differentiation in vitro.
引用
收藏
页码:277 / 283
页数:7
相关论文
共 35 条
[11]   Role of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle [J].
Hara, T ;
Kamura, T ;
Kotoshiba, S ;
Takahashi, H ;
Fujiwara, K ;
Onoyama, I ;
Shirakawa, M ;
Mizushima, N ;
Nakayama, KI .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (21) :9292-9303
[12]   Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export [J].
Ishida, N ;
Hara, T ;
Kamura, T ;
Yoshida, M ;
Nakayama, K ;
Nakayama, KI .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (17) :14355-14358
[13]   The POU factor Oct-6 and Schwann cell differentiation [J].
Jaegle, M ;
Mandemakers, W ;
Broos, L ;
Zwart, R ;
Karis, A ;
Visser, P ;
Grosveld, F ;
Meijer, D .
SCIENCE, 1996, 273 (5274) :507-510
[14]   Signals that determine Schwann cell identity [J].
Jessen, KR ;
Mirsky, R .
JOURNAL OF ANATOMY, 2002, 200 (04) :367-375
[15]   Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase [J].
Kamura, T ;
Hara, T ;
Matsumoto, M ;
Ishida, N ;
Okumura, F ;
Hatakeyama, S ;
Yoshida, M ;
Nakayama, K ;
Nakayama, KI .
NATURE CELL BIOLOGY, 2004, 6 (12) :1229-1235
[16]   Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1) [J].
Kiyokawa, H ;
Kineman, RD ;
ManovaTodorova, KO ;
Soares, VC ;
Hoffman, ES ;
Ono, M ;
Khanam, D ;
Hayday, AC ;
Frohman, LA ;
Koff, A .
CELL, 1996, 85 (05) :721-732
[17]   Molecular dissection of the interaction between p27 and Kip1 ubiquitylation-promoting complex, the ubiquitin ligase that regulates proteolysis of p27 in G1 phase [J].
Kotoshiba, S ;
Kamura, T ;
Hara, T ;
Ishida, N ;
Nakayama, KI .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (18) :17694-17700
[18]   MICE DEFICIENT FOR RB ARE NONVIABLE AND SHOW DEFECTS IN NEUROGENESIS AND HEMATOPOIESIS [J].
LEE, EYHP ;
CHANG, CY ;
HU, NP ;
WANG, YCJ ;
LAI, CC ;
HERRUP, K ;
LEE, WH ;
BRADLEY, A .
NATURE, 1992, 359 (6393) :288-294
[19]   Lack of replicative senescence in normal rodent glia [J].
Mathon, NF ;
Malcolm, DS ;
Harrisingh, MC ;
Cheng, LL ;
Lloyd, AC .
SCIENCE, 2001, 291 (5505) :872-875
[20]   LINGO-1 negatively regulates myelination by oligodendrocytes [J].
Mi, S ;
Miller, RH ;
Lee, X ;
Scott, ML ;
Shulag-Morskaya, S ;
Shao, ZH ;
Chang, JF ;
Thill, G ;
Levesque, M ;
Zhang, MD ;
Hession, C ;
Sah, D ;
Trapp, B ;
He, ZG ;
Jung, V ;
McCoy, JM ;
Pepinsky, RB .
NATURE NEUROSCIENCE, 2005, 8 (06) :745-751