Cytoplasmic p21Cip1/WAF1 regulates neurite remodeling by inhibiting Rho-kinase activity

Tanaka, Hiroyuki; Yamashita, Toshio; Asada, Minoru; Mizutani, Shuki; Yoshikawa, Hideki; Tohyama, Masaya

doi:10.1083/jcb.200202071

Cited by 148 publications

(142 citation statements)

References 54 publications

Supporting

Mentioning

135

Contrasting

Unclassified

Order By: Relevance

“…A role for cytosolic p21 has also been demonstrated in neuronal differentiation. After functioning in the nucleus to block cell proliferation, cytoplasmic p21 promotes neuronal differentiation where it regulates Rho-induced actin remodeling leading to neurite outgrowth (38). Cytoplasmic p21 has also been shown recently (39) to enhance axonal regeneration and functional recovery after spinal cord injury.…”

Section: Discussionmentioning

confidence: 99%

Mirk/Dyrk1B Mediates Survival during the Differentiation of C2C12Myoblasts

Mercer

Ewton

Deng

et al. 2005

Journal of Biological Chemistry

110

View full text Add to dashboard Cite

The kinase Mirk/dyrk1B is essential for the differentiation of C2C12 myoblasts. Mirk reinforces the G 0 /G 1 arrest state in which differentiation occurs by directly phosphorylating and stabilizing p27Kip1 and destabilizing cyclin D1. We now demonstrate that Mirk is antiapoptotic in myoblasts. Knockdown of endogenous Mirk by RNA interference activated caspase 3 and decreased myoblast survival by 75%, whereas transient overexpression of Mirk increased cell survival. Mirk exerts its anti-apoptotic effects during muscle differentiation at least in part through effects on the cell cycle inhibitor and pro-survival molecule p21Cip1 . Overexpression and RNA interference experiments demonstrated that Mirk phosphorylates p21 within its nuclear localization domain at Ser-153 causing a portion of the typically nuclear p21 to localize in the cytoplasm. Phosphomimetic GFP-p21-S153D was pancellular in both cycling C2C12 myoblasts and NIH3T3 cells. Endogenous Mirk in myotubes and overexpressed Mirk in NIH3T3 cells were able to cause the pancellular localization of wild-type GFPp21 but not the nonphosphorylatable mutant GFP-p21-S153A. Translocation to the cytoplasm enables p21 to block apoptosis through inhibitory interaction with pro-apoptotic molecules. Phosphomimetic p21-S153D was more effective than wild-type p21 in blocking the activation of caspase 3. Transient expression of p21-S153D also increased myoblast viability in colony forming assays, whereas the p21-S153A mutant had no effect. This Mirk-dependent change in p21 intracellular localization is a natural part of myoblast differentiation. Endogenous p21 localized exclusively to the nuclei of proliferating myoblasts but was also found in the cytoplasm of post-mitotic multinucleated myotubes and adult human skeletal myofibers.

show abstract

Section: Discussionmentioning

confidence: 99%

Mirk/Dyrk1B Mediates Survival during the Differentiation of C2C12Myoblasts

Mercer

Ewton

Deng

et al. 2005

Journal of Biological Chemistry

110

View full text Add to dashboard Cite

show abstract

“…Similarly, cytoplasmic p21 was reported to have a much lower capacity to arrest the cell cycle (16). Tanaka et al (20) have reported that cytoplasmic p21 regulates neurite remodeling by inhibiting Rho-kinase activity. These findings suggest that cytoplasmic p21 plays a specific role.…”

Section: Discussionmentioning

confidence: 99%

Prognostic implications of p21 (Waf1/Cip1) immunolocalization in multiple myeloma

et al. 2005

View full text Add to dashboard Cite

Protein p21 (Waf1/Cip1) plays a critical role in controlling the cell cycle especially as a check point of G1 and is intimately associated with important cellular activities including differentiation, senescence, tumorigenesis, and apoptosis. In the present study, we examined the expression of p21 in multiple myeloma (MM) cells for prognostic evaluation. The immunocytochemical localization of p21 could be categorized into nuclear and cytoplasmic types. The nuclear-type p21 localization was correlated with the severity of MM and the expression of proliferating cell nuclear antigen and p53. Patients with the nuclear-type p21 localization survived significantly shorter than those with the cytoplasmic-type localization. Thus, the present study suggests that p21-immunolocalization can be a useful prognostic marker of MM.

show abstract

“…Therefore, the relative levels of cyclins, CDKs and CDKIs determine whether cell-cycle progression will occur. In addition, CDKIs may influence actin cytoskeletal structures and cell motility by attenuating Rho signalling; for example, p27 directly binds and inhibits RhoA (Besson et al, 2004), whereas p21 and p57 have been reported to inhibit downstream signalling by inhibiting ROCK (Tanaka et al, 2002;Lee and Helfman, 2004) and LIM (Yokoo et al, 2003) kinases, respectively.…”

Section: Ink4c and P19mentioning

confidence: 99%