The ink4a/arf Tumor Suppressors Cooperate with p21  in the Processes of Mouse Epidermal Differentiation, Senescence, and Carcinogenesis

Paramio, Jesús M.; Segrelles, Carmen; Ruíz, Sergio; Juan, Manel; Page, Angustias; Martínez, J. Larrauri; Serrano, Manuel; Jorcano, José L.

doi:10.1074/jbc.m105650200

Cited by 47 publications

(59 citation statements)

References 56 publications

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“…With some exceptions (Paramio et al, 2001;Weinberg et al, 1997), previous studies support an anti-tumor function of p21 Cip1 . However, disagreement exists regarding the effects of p21 Cip1 loss on tumor formation.…”

Section: Discussionmentioning

confidence: 90%

Loss of the cell cycle inhibitors p21Cip1 and p27Kip1 enhances tumorigenesis in knockout mouse models

et al. 2002

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Events that contribute to tumor formation include mutations in the ras gene and loss or inactivation of cell cycle inhibitors such as p21 Cip1 and p27 Kip1 . In our previous publication, we showed that mice expressing the MMTV/v-Ha-ras transgene developed tumors earlier and at higher multiplicities in the absence than in the presence of p21 Cip1 . To further evaluate the combinatorial role of genetic alterations and loss of cell cycle inhibitors in tumorigenesis, we performed two companion studies. In the first study, wild type and p21 Cip1 -null mice were exposed to the chemical carcinogen, urethane. Similar to its effects in v-Ha-ras mice, loss of p21 Cip1 accelerated tumor onset and increased tumor multiplicity in urethane-treated mice. Lung tumors were the predominant tumor type in urethane-treated mice regardless of p21 Cip1 status. In the second study, tumor formation was monitored in v-Ha-ras mice expressing or lacking p27 Kip1 . Unlike p21 Cip1 , the absence of p27 Kip1 had no effect on the timing or multiplicity of tumor formation, which was largely restricted to mammary and salivary glands. However, once tumors appeared, they grew faster in p27 Kip1 -null mice than in p27 Kip1 -wild type mice. Increases in growth rate were particularly striking for salivary tumors in ras/p27 7/7 mice. Loss of p21 Cip1 , on the other hand, had no effect on tumor growth rate in v-Ha-ras mice. Collectively, our data suggest that p21 Cip1 suppresses tumor formation elicited by multiple agents and that p21 Cip1 and p27 Kip1 suppress tumor formation in different ways.

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Section: Discussionmentioning

confidence: 90%

Loss of the cell cycle inhibitors p21Cip1 and p27Kip1 enhances tumorigenesis in knockout mouse models

et al. 2002

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“…On the other hand, by interfering with MDM2 (mouse double minute 2)‐dependent degradation of p53, p14/p19 ARF controls p53/p21 WAF1 ‐induced G1 or G2 cell cycle arrest (Gil & Peters, 2006). Remarkably, using knockout mice models for this locus, it was possible to reveal that these senescence features could be associated with the terminal differentiation program in some specific cell types including keratinocytes (Paramio et al ., 2001; Bachoo et al ., 2002), chondrocytes (Philipot et al ., 2014), myofibers (Pajcini et al ., 2010), and also megakaryocytic cells (Muñoz‐Espín & Serrano, 2014). Megakaryocytic cells, myeloid‐derived immune cells from which blood platelets originate, are required for wound healing and immune responses (Besancenot et al ., 2010), opening new avenues to explore features of senescence in other types of immune cells.…”

Section: Cellular Senescence and Immune Cell Fate Decisionmentioning

confidence: 99%

Cellular senescence impact on immune cell fate and function

et al. 2016

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SummaryCellular senescence occurs not only in cultured fibroblasts, but also in undifferentiated and specialized cells from various tissues of all ages, in vitro and in vivo. Here, we review recent findings on the role of cellular senescence in immune cell fate decisions in macrophage polarization, natural killer cell phenotype, and following T‐lymphocyte activation. We also introduce the involvement of the onset of cellular senescence in some immune responses including T‐helper lymphocyte‐dependent tissue homeostatic functions and T‐regulatory cell‐dependent suppressive mechanisms. Altogether, these data propose that cellular senescence plays a wide‐reaching role as a homeostatic orchestrator.

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“…The p21 was found not to be involved in the regulation of differentiation of the mouse skin tumours [74] and in mouse keratinocytes [75] . In the p21 null mice, normal differentiation has been observed thus implying that p21 is not a mutually exclusive agent that promotes differentiation [76] . Various other genes are thought to be involved and maybe cooperate with p21 to regulate differentiation including p15 [76] , p16 [77] , p18 [76] , p19 [76] , p27 [77] , p53 [78] , p57 [79] and Rb [78] .…”

Section: P21 and Differentiationmentioning

confidence: 99%

The Biology of p21Waf1/Cip1 - Review Paper

Blundell¹

2006

American J. of Biochemistry and Biotechnology

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p21WAF1/Cip1 belongs to the Cip/Kip family of cyclin kinase inhibitors (CKI) (p21 Waf1/Cip1 , p27Kip1 , p57 Kip1 ). p21 Waf1/Cip1 was first described as a potent and universal inhibitor of cyclin-dependent kinases (Cdks). Two forms of functionally active p21 has been localized and described: a nuclear and a cytoplasmic forms. In this paper the structures of p21 has been described and as well as it functional biology in terms of differentiation, proliferation and apoptotic activities. The upregulation of p21 by p53-dependent and p53-independent mechanisms is also described.

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The ink4a/arf Tumor Suppressors Cooperate with p21 in the Processes of Mouse Epidermal Differentiation, Senescence, and Carcinogenesis

Cited by 47 publications

References 56 publications

Loss of the cell cycle inhibitors p21Cip1 and p27Kip1 enhances tumorigenesis in knockout mouse models

Loss of the cell cycle inhibitors p21Cip1 and p27Kip1 enhances tumorigenesis in knockout mouse models

Cellular senescence impact on immune cell fate and function

The Biology of p21Waf1/Cip1 - Review Paper

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