FIP200 (focal adhesion kinase family interacting protein of 200 kDa) has been shown to interact with other proteins to regulate several intracellular signaling pathways. To study a potential role of FIP200 in tumorigenesis and possibly other disease processes in vivo, we created and analyzed murine mammary tumor virus-Cre-mediated FIP200 conditional knock-out (CKO) mice. We found that deletion of FIP200 in mammary epithelial cells did not result in spontaneous development of breast cancer. Moreover, deletion of FIP200 did not further accelerate or inhibit lymphomagenesis induced by inactivation of p53 in mice. Interestingly, however, FIP200 and p53 double conditional knock-out (dCKO) mice exhibited significant hyperplasia of epidermis (acanthosis), thickening of the cornified layer (hyperkeratosis), and increased vascularity in the dermis. FIP200 CKO mice also showed similar, although less severe, skin defects as dCKO mice. Analyses of primary keratinocytes isolated from dCKO mice did not detect increased proliferation of these cells in vitro, suggesting that epidermis hyperproliferation is not epidermal cell-autonomous but may be a consequence of increased inflammation triggered by immune cells in vivo. Consistent with this possibility, we found infiltration of leukocytes including T cells, macrophages, and granulocytes into the dermis and epidermis, associated with activation of NF-κB and increased expression of several proinflammatory cytokines and chemokines in skin of the dCKO mice. We further found that cultured FIP200 KO keratinocytes showed reduced NF-κB phosphorylation in response to tumor necrosis factor α stimulation, suggesting a paracrine regulation of aberrant NF-κB activation in the skin microenviroment of dCKO and FIP200 CKO mice. Together, these results demonstrate that ablation of FIP200, although not promoting tumorigenesis, can lead to skin inflammatory disorders, suggesting a novel function of FIP200 in the maintenance of normal skin homeostasis in vivo. FIP200 (focal adhesion kinase family interacting protein of 200 kDa) has been shown to interact with other proteins to regulate several intracellular signaling pathways. To study a potential role of FIP200 in tumorigenesis and possibly other disease processes in vivo, we created and analyzed murine mammary tumor virus-Cre-mediated FIP200 conditional knock-out (CKO) mice. We found that deletion of FIP200 in mammary epithelial cells did not result in spontaneous development of breast cancer. Moreover, deletion of FIP200 did not further accelerate or inhibit lymphomagenesis induced by inactivation of p53 in mice. Interestingly, however, FIP200 and p53 double conditional knock-out (dCKO) mice exhibited significant hyperplasia of epidermis (acanthosis), thickening of the cornified layer (hyperkeratosis), and increased vascularity in the dermis. FIP200 CKO mice also showed similar, although less severe, skin defects as dCKO mice. Analyses of primary keratinocytes isolated from dCKO mice did not detect increased proliferation of these cells in vitro, suggesting that epidermis hyperproliferation is not epidermal cell-autonomous but may be a consequence of increased inflammation triggered by immune cells in vivo. Consistent with this possibility, we found infiltration of leukocytes including T cells, macrophages, and granulocytes into the dermis and epidermis, associated with activation of NF-κB and increased expression of several proinflammatory cytokines and chemokines in skin of the dCKO mice. We further found that cultured FIP200 KO keratinocytes showed reduced NF-κB phosphorylation in response to tumor necrosis factor α stimulation, suggesting a paracrine regulation of aberrant NF-κB activation in the skin microenviroment of dCKO and FIP200 CKO mice. Together, these results demonstrate that ablation of FIP200, although not promoting tumorigenesis, can lead to skin inflammatory disorders, suggesting a novel function of FIP200 in the maintenance of normal skin homeostasis in vivo. Focal adhesion kinase family interacting protein of 200 kDa (FIP200) 4The abbreviations used are: FIP200, focal adhesion kinase family interacting protein of 200 kDa; KO, knock-out; TNF, tumor necrosis factor; dCKO, double conditional knock-out; CKO, conditional knock-out; DAPI, 4,6-diamidino-2-phenylindole; BrdU, 5-bromo-2′-deoxyuridine; JNK, c-Jun NH2-terminal kinase; MMTV, murine mammary tumor virus; IL, interleukin; IFN, interferon. was originally identified by us as an inhibitor of focal adhesion kinase and its related kinase Pyk2 (1Abbi S. Ueda H. Zheng C. Cooper L.A. Zhao J. Christopher R. Guan J.L. Mol. Biol. Cell. 2002; 13: 3178-3191Crossref PubMed Scopus (98) Google Scholar, 2Ueda H. Abbi S. Zheng C. Guan J.L. J. Cell Biol. 2000; 149: 423-430Crossref PubMed Scopus (63) Google Scholar). Shortly after these studies, FIP200 was also identified by Chano and colleagues (3Chano T. Ikegawa S. Kontani K. Okabe H. Baldini N. Saeki Y. Oncogene. 2002; 21: 1295-1298Crossref PubMed Scopus (62) Google Scholar) as a potential regulator of the RB1 gene (designated as RB1CC1 for RB1-inducible coiled-coil 1). Chano et al. (4Chano T. Kontani K. Teramoto K. Okabe H. Ikegawa S. Nat. Genet. 2002; 31: 285-288Crossref PubMed Scopus (67) Google Scholar) further showed that 20% of primary breast cancers that they screened contained large deletion mutations in FIP200 that are predicted to generate markedly truncated proteins. In addition, we found that overexpression of FIP200 inhibited cell cycle progression through regulation of both cyclin D1 and cyclin-dependent kinase inhibitor p21 in breast cancer cells (5Melkoumian Z.K. Peng X. Gan B. Wu X. Guan J.L. Cancer Res. 2005; 65: 6676-6684Crossref PubMed Scopus (72) Google Scholar). Based on these initial studies, FIP200 was suggested to function as a potential tumor suppressor (4Chano T. Kontani K. Teramoto K. Okabe H. Ikegawa S. Nat. Genet. 2002; 31: 285-288Crossref PubMed Scopus (67) Google Scholar). Recent studies have shown that FIP200 interacts with a number of other proteins besides FAK and Pyk2 and regulates several signaling pathways and cellular processes (6Gan B. Guan J.L. Cell. Signal. 2008; 20: 787-794Crossref PubMed Scopus (59) Google Scholar). We have identified an interaction between FIP200 and TSC1 and showed that this interaction negatively regulates TSC1-TSC2 complex function to increase mammalian target of rapamycin activation and cell growth (7Gan B. Melkoumian Z.K. Wu X. Guan K.L. Guan J.L. J. Cell Biol. 2005; 170: 379-389Crossref PubMed Scopus (76) Google Scholar). FIP200 was also shown to regulate the size of muscle cells through its activation of mammalian target of rapamycin signaling (8Chano T. Saji M. Inoue H. Minami K. Kobayashi T. Hino O. Okabe H. Int. J. Mol. Med. 2006; 18: 425-432PubMed Google Scholar). Martin et al. (9Martin N. Schwamborn K. Urlaub H. Gan B. Guan J.L. Dejean A. Mol. Cell. Biol. 2008; 28: 2771-2781Crossref PubMed Scopus (20) Google Scholar) found recently that association of PIASy with FIP200 increased nuclear localization of FIP200, reducing its cytoplasmic pool and consequently its activity in the inhibition of TSC complex. Conversely, FIP200 enhanced the transcriptional activation of the p21 promoter by PIASy by co-recruitment of both proteins to the promoter as detected by chromatin immunoprecipitation analysis (9Martin N. Schwamborn K. Urlaub H. Gan B. Guan J.L. Dejean A. Mol. Cell. Biol. 2008; 28: 2771-2781Crossref PubMed Scopus (20) Google Scholar). Furthermore, a very recent study showed that FIP200 interacts with ULK1 and -2, mammalian orthologs of the yeast Atg1 protein, which are components of autophagosome essential for its formation (10Hara T. Takamura A. Kishi C. Iemura S. Natsume T. Guan J.L. Mizushima N. J. Cell Biol. 2008; 181: 497-510Crossref PubMed Scopus (725) Google Scholar). FIP200 itself was redistributed to autophagosomes upon induction of autophagy by starvation. Moreover, autophagy induction by various treatments was abolished in FIP200-null mouse embryonic fibroblasts, suggesting that FIP200 may function as a novel regulator of autophagy through its interaction with ULK1 and -2 in mammalian cells. FIP200 is widely expressed in various human tissues (11Bamba N. Chano T. Taga T. Ohta S. Takeuchi Y. Okabe H. Int. J. Mol. Med. 2004; 14: 583-587PubMed Google Scholar) and is an evolutionarily conserved protein present in human, mouse, rat, frog, fly, and worm. The high degree of conservation during evolution suggests potentially important functions of FIP200 in vivo. Consistent with this, we showed recently that total knock-out (KO) of FIP200 in mice resulted in embryonic lethality at mid/late gestation associated with heart failure and liver degeneration (12Gan B. Peng X. Nagy T. Alcaraz A. Gu H. Guan J.L. J. Cell Biol. 2006; 175: 121-133Crossref PubMed Scopus (180) Google Scholar). As expected based on studies in vitro, FIP200 KO mice showed increased activity of the TSC1-TSC2 complex and reduced cell size in the developing heart, which are associated with the severe defects in the myocardium with thinner ventricular walls. Furthermore, FIP200 KO embryos exhibited significant apoptosis in heart and liver, suggesting a role for FIP200 in the regulation of cell survival and FIP200 KO mouse embryonic and liver cells exhibited an to tumor necrosis factor apoptosis to activation of the signaling analysis showed that FIP200 interact with and as a to signaling to activation induced by (12Gan B. Peng X. Nagy T. Alcaraz A. Gu H. Guan J.L. J. Cell Biol. 2006; 175: 121-133Crossref PubMed Scopus (180) Google Scholar). may the increased of FIP200 KO cells to apoptosis and also possibly for the increased apoptosis in FIP200 KO To the embryonic lethality of the total KO of FIP200 and to the potential role of FIP200 in tumorigenesis and other processes in vivo, we and analyzed FIP200 conditional KO mice by which FIP200 deletion in mammary epithelial cells and several other cells including keratinocytes A. M. Res. PubMed Scopus Google Scholar, K. T. B. R. Res. PubMed Scopus Google Scholar). We found that inactivation of FIP200 mammary tumor development lymphomagenesis induced by of p53 in suggesting that FIP200 may not function as a tumor suppressor as in we found that the FIP200 and p53 double conditional KO (dCKO) mice as as FIP200 conditional KO (CKO) mice a inflammatory skin that is by epidermal of and epidermal and and of PubMed Scopus Google Scholar). We also found an activation of the NF-κB and of cytokines and in the skin of the which are also of in human We further found that cultured FIP200 KO keratinocytes showed reduced NF-κB phosphorylation in response to stimulation, suggesting a paracrine regulation of aberrant NF-κB activation in the skin microenviroment of dCKO and FIP200 CKO mice. results a role for FIP200 in the maintenance of normal skin homeostasis and skin inflammatory in vivo. and mice A. M. Res. PubMed Scopus Google Scholar, K. T. B. R. Res. PubMed Scopus Google Scholar) from of of mice J. R. H. H. M. A. Nat. Genet. PubMed Scopus Google Scholar) and mice Nat. Genet. 21: PubMed Scopus Google Scholar) from FIP200 mice (12Gan B. Peng X. Nagy T. Alcaraz A. Gu H. Guan J.L. J. Cell Biol. 2006; 175: 121-133Crossref PubMed Scopus (180) Google Scholar). for of mice and for by analysis of isolated from as for the X. H. R. Alcaraz A. J. K. Gu H. Guan J.L. J. 2006; PubMed Scopus Google for the and FIP200 or FIP200 (12Gan B. Peng X. Nagy T. Alcaraz A. Gu H. Guan J.L. J. Cell Biol. 2006; 175: 121-133Crossref PubMed Scopus (180) Google and for and p53 or p53 J. R. H. H. M. A. Nat. Genet. PubMed Scopus Google Scholar). the by the and at the of and in with and and of from mice was in at The epidermis was from dermis and with to The was by the of inhibitor keratinocytes cultured on with and in with and was isolated from skin to the to with as The to are upon and in and in and with and skin in and on was with the primary and from Cell factor and to or with for of with of and after was on the to the or cultured keratinocytes in and with inhibitor and protein by analysis was as H. X. Gan B. Melkoumian Z.K. Guan J.L. Zhao J. J. Biol. 2006; PubMed Scopus (67) Google Scholar). in in at several in in the was in double to and by for The was in of in and in The in and with and lead The a at a was used to of between was KO of FIP200 by studies mutations of the FIP200 gene in 20% human breast cancer screened that FIP200 may function as a tumor suppressor (4Chano T. Kontani K. Teramoto K. Okabe H. Ikegawa S. Nat. Genet. 2002; 31: 285-288Crossref PubMed Scopus (67) Google Scholar). To study a potential role and of FIP200 in breast we FIP200 conditional KO mice and FIP200 CKO by the FIP200 mice (12Gan B. Peng X. Nagy T. Alcaraz A. Gu H. Guan J.L. J. Cell Biol. 2006; 175: 121-133Crossref PubMed Scopus (180) Google Scholar) with the mice A. M. Res. PubMed Scopus Google Scholar, K. T. B. R. Res. PubMed Scopus Google Scholar). FIP200 CKO mice and normal and from at the from mammary of FIP200 CKO and mice a and analyzed by deletion of FIP200 in mammary of FIP200 CKO as mammary or other in FIP200 CKO mice during of suggesting that inactivation of FIP200 not mice to breast or other cancers in this mouse We the potential of of FIP200 with mutations in other tumor suppressor p53 is a tumor suppressor and of human mutations or deletion of the p53 To the of FIP200 accelerate tumorigenesis, we the p53 into FIP200 CKO mice and mice with the (designated as dCKO as as mice with and as p53 CKO of mice cancer of the mice in with by of other p53 deletion did not tumor at this not showed that the was also found in the liver, and not in of mice. breast detected in these mice to is on analysis of conditional KO of p53 total KO of p53 is to in mice T. S. Biol. PubMed Scopus Google the that mice in studies to expression of in other cells as T To this possibility, from of dCKO, p53 CKO, or mice and analyzed by a reduced expression of p53 in from both p53 CKO and dCKO mice and the of FIP200 in a from dCKO which are with activity of in the to deletion of the p53 and FIP200 in these mice. To further this possibility, protein from and to expression of FIP200 in the from p53 CKO mice but not from dCKO mice As p53 is in these results that of FIP200 not accelerate or inhibit tumorigenesis induced by p53 inactivation in mouse of an in dCKO and FIP200 CKO the of of dCKO and p53 CKO we that by after the dCKO not p53 mice to and with and a and although the skin of these mice from the at not The dCKO mice a skin 20% of these mice showed severe at or with skin at of skin from dCKO mice epidermal thickening with p53 CKO mice not of dCKO mice showed a epidermis by and and In severe epidermal of in the layer of the epidermis In addition, exhibited epidermal into that into the dermis and from these skin we did not in the liver, heart, and in dCKO mice by of not the skin defects of in dCKO mice and both dCKO and p53 CKO mice to a these results that skin defects in dCKO mice is a consequence of FIP200 deletion in the by to tumorigenesis in these mice. p53 CKO mice did not of the skin defects in the dCKO results that conditional KO of FIP200 is for the we further the potential defects in the skin of FIP200 CKO although of the mice exhibited the severe skin as in of dCKO mice that initial on skin FIP200 CKO mice also showed and with the FIP200 mice as a a and analysis of skin showed epidermal hyperplasia in FIP200 CKO mice with the mice and that deletion of FIP200 also similar, skin defects as the dCKO mice. has been to be in the skin in studies A. M. Res. PubMed Scopus Google Scholar, K. T. B. R. Res. PubMed Scopus Google deletion of the FIP200 in the To further a in dCKO we mice used in study with the mice in which expression of of a Nat. Genet. 21: PubMed Scopus Google Scholar). As shown in activity was detected in mammary epithelial cells and several other tissues including skin and not but or in heart liver, and not Consistent with these analysis of from skin showed expression of FIP200 in dCKO mice with p53 CKO mice results further that skin in dCKO and FIP200 CKO mice are by FIP200 deletion in keratinocytes by and in the of dCKO and FIP200 CKO in the the skin defects in dCKO we analyzed proliferation of keratinocytes of hyperplasia in the from dCKO mice and p53 CKO mice that been with to and by with to a markedly increased at the layer of the epidermis in dCKO mice with p53 CKO mice. of the by also increased proliferation of keratinocytes in dCKO mice Interestingly, increased apoptosis was also found the skin of dCKO mice as by for In addition, we found an increase in the number of with and as detected by with factor in the dermis of the dCKO mice for proliferation or also showed increased proliferation of keratinocytes in FIP200 CKO mice and with and also increased apoptosis and in these mice and with from these results that deletion of FIP200 to a hyperproliferation may be epidermal cell or as a response to the of inflammatory leukocytes M. M. M. A. A. M. M. R. A. T. K. 2002; PubMed Scopus Google Scholar, S. 2004; 18: PubMed Scopus Google Scholar). To deletion of FIP200 to epidermal hyperproliferation through increased potential of keratinocytes in dCKO primary epidermal keratinocytes isolated from dCKO and p53 CKO mice and analyzed in however, we found that keratinocytes from dCKO mice showed a reduced growth with that from p53 CKO mice these analysis an in the number of cells a of in Consistent with this, of the cells with also a in the number of keratinocytes isolated from dCKO mice with that from p53 CKO mice keratinocytes from both dCKO and p53 CKO mice did not a significant in apoptosis cultured on with and in growth results suggested that deletion of FIP200 did not lead to increased proliferation of epidermal keratinocytes in and that epidermal hyperproliferation in may not be of into and of epidermal hyperplasia be by infiltration of inflammatory cells, we the of leukocytes in the skin of dCKO and p53 CKO mice by various for these cells. with which is a the of leukocytes in the dermis and epidermis of dCKO but not in p53 CKO mice with a T cell showed a significant increase of T cells in the dermis of dCKO mice with that of p53 CKO mice with and for and also the infiltration of these immune cells in the skin of dCKO mice and also that the dermis of dCKO mice was with immune cells with and The of the inflammatory cells detected in the and also found in the epidermis of dCKO mice. Furthermore, infiltration can be detected in the skin of dCKO mice at of skin has not in these mice not leukocytes including T cells, macrophages, and granulocytes also detected in the skin of FIP200 CKO mice Together, these results that deletion of FIP200 to inflammation in the skin of dCKO and FIP200 CKO which is for epidermal hyperplasia in these mice. of NF-κB and of and in the NF-κB a role in inflammation Nat. 2002; PubMed Scopus Google Scholar, N. T. PubMed Scopus Google we the activation of NF-κB by phosphorylation of the of NF-κB in the skin of dCKO mice. As shown in analysis of from the skin a significant increase of phosphorylation in the skin of dCKO mice with that from p53 CKO mice of skin also identified NF-κB in the dermis of dCKO but not in p53 CKO mice Consistent with the localization of of the with showed with and activation of NF-κB in the NF-κB was also found in the dermis of FIP200 CKO mice but not in mice results that activation of the NF-κB signaling in leukocytes may a role in inflammation and of dCKO and FIP200 CKO mice. studies have shown that NF-κB signaling inflammation by transcriptional activation of a number of proinflammatory cytokines including and M. Nat. 2005; PubMed Scopus Google Scholar). we further analyzed the expression of various cytokines and chemokines in skin inflammation by As shown in skin from dCKO mice expressed of proinflammatory cytokines including and which have been in the of M. T. J. PubMed Scopus Google Scholar, C. N. J. Med. PubMed Scopus Google Scholar, O. M. S. 2005; PubMed Scopus Google Scholar). The dCKO skin also showed expression of inflammatory protein and and In and expressed in in the skin from dCKO and p53 CKO mice. results that activation of NF-κB in leukocytes may of proinflammatory cytokines and cytokines the dermis may proliferation of keratinocytes the epidermal and further the activation of NF-κB possibly as a which for inflammatory response and epidermal proliferation in the skin of mice FIP200 to NF-κB in studies suggested that of signaling pathways in the epidermis a skin inflammatory M. M. M. A. A. M. M. R. A. T. K. 2002; PubMed Scopus Google Scholar, A. M. K. K. T. N. T. J. 2006; PubMed Scopus Google Scholar). We NF-κB activation by in isolated As in of NF-κB activation by is reduced in dCKO keratinocytes with p53 CKO cells, as by phosphorylation of its Furthermore, activation of NF-κB upon is also in FIP200 CKO keratinocytes with the keratinocytes Together, these results that deletion of FIP200 NF-κB activation in which may be for increased of leukocytes into the dermis to the skin inflammatory in the FIP200 CKO and dCKO mice. a conditional KO we present suggesting that FIP200 is in skin inflammatory of human of FIP200 or with p53 to skin including as as infiltration of inflammatory leukocytes into the dermis and epidermis by increased vascularity in the mice. Furthermore, the mice showed activation of NF-κB and of proinflammatory cytokines and in the which are also in of human is the inflammatory of skin and in of the is by a epidermal hyperplasia by of in the epidermal formation of the and skin infiltration of inflammatory cells as cells, macrophages, and cells PubMed Scopus Google Scholar). between the immune and various cells in the skin have been shown to in the development of inflammatory skin J. PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar). of cytokines and growth by fibroblasts, and immune cells is for the maintenance of skin homeostasis A. N. S. A. M. Cell. 2000; PubMed Scopus Google Scholar, M. Cell. 2006; PubMed Scopus Google Scholar). In the NF-κB signaling has been shown to an essential role in of inflammation as Nat. 2002; PubMed Scopus Google Scholar, N. T. PubMed Scopus Google Scholar). studies have mouse that of T. Nat. Med. PubMed Google Scholar, A. M. H. J. PubMed Scopus Google including mice T. J. PubMed Scopus Google Cell. PubMed Scopus Google or S. S. J. M. K. S. J. Nat. Med. 2005; PubMed Scopus Google Scholar) in the epidermis as as conditional KO of Mol. Cell. Biol. PubMed Google Scholar, B. B. S. K. R. S. J.L. R. A. T. M. K. PubMed Scopus Google Scholar) and M. M. M. A. A. M. M. R. A. T. K. 2002; PubMed Scopus Google Scholar, A. M. K. K. T. N. T. J. 2006; PubMed Scopus Google Scholar). of these have been in the regulation of NF-κB signaling pathways or and in NF-κB have been in of the mouse Interestingly, these studies that the inhibition or activation of NF-κB signaling can lead to skin inflammation to we in the dCKO and FIP200 CKO mice. suggests that skin homeostasis a NF-κB studies suggested that inactivation of FIP200 did not NF-κB signaling in mouse embryonic (12Gan B. Peng X. Nagy T. Alcaraz A. Gu H. Guan J.L. J. Cell Biol. 2006; 175: 121-133Crossref PubMed Scopus (180) Google analysis showed activation of NF-κB in keratinocytes isolated from dCKO or FIP200 CKO suggesting a function of FIP200 in the regulation of NF-κB signaling in these cells. ablation of FIP200 from keratinocytes with the of NF-κB as an inflammatory response that is by infiltration of immune cells, activation of NF-κB in these cells, and induction of inflammatory cytokines as and in skin in the development of skin inflammation disease in the mice. mammary and skin cells, also exhibited activity in several other cell including of cells as and of and cells H. S. Cell. PubMed Scopus Google Scholar, A. J. PubMed Scopus Google Scholar). increased infiltration of inflammatory cells be the consequence of immune cell activation upon FIP200 deletion in of these cells. this is not we did not significant inflammation in other tissues in these mice. Consistent with this, we did not in the spontaneous activation of from FIP200 CKO mice with from as by expression Furthermore, in the activation of NF-κB in the and of FIP200 CKO mice with mice and T cells, and granulocytes also important in skin although has not been in these cells. We found that FIP200 was not in primary isolated from FIP200 CKO to the of activity in these cells results that the primary of the inflammatory of the FIP200 CKO and dCKO mice is to FIP200 deletion in but not to of various immune cells. be that although they are not the primary for the other leukocytes a role in skin inflammation in FIP200 CKO mice. studies conditional KO mice showed that of macrophages, but not granulocytes or T cells, from these mice abolished the skin suggesting an essential of in the skin by inhibition of NF-κB signaling upon deletion of in the skin A. M. K. K. T. N. T. J. 2006; PubMed Scopus Google Scholar). In an FIP200 deletion in keratinocytes and inhibition of the NF-κB into the dermis of immune cells as and activation by as to be inflammatory cells with increased NF-κB signaling may and cytokines to which epidermal keratinocytes the activation of NF-κB in the skin of dCKO and FIP200 CKO mice a paracrine NF-κB signaling between epidermal keratinocytes and various inflammatory cells that may increase with S. H. Cell Biol. PubMed Scopus Google which is with of severe skin in or mice a is in FIP200 has been as a tumor suppressor based on initial studies on breast cancer cells and analysis of mutations of FIP200 in human breast cancer (4Chano T. Kontani K. Teramoto K. Okabe H. Ikegawa S. Nat. Genet. 2002; 31: 285-288Crossref PubMed Scopus (67) Google Scholar). for a tumor suppressor role of FIP200 in is and the embryonic lethality of FIP200 total KO mice its as a to the function of FIP200 in In this deletion of FIP200 did not accelerate or inhibit lymphomagenesis upon inactivation of p53 in mice. FIP200 is to function as a tumor suppressor in vivo, suggesting a (4Chano T. Kontani K. Teramoto K. Okabe H. Ikegawa S. Nat. Genet. 2002; 31: 285-288Crossref PubMed Scopus (67) Google Scholar). these not the that FIP200 may as a tumor suppressor in with other gene In we that the ablation of FIP200 is for tumorigenesis induced by p53 but skin epidermal hyperplasia and inflammation in mouse studies novel into the of inflammatory skin disease and also be of to other inflammatory The dCKO and FIP200 CKO mice may mouse for and for the of inflammatory skin in We are to colleagues and for of the and and for with We for p53 mice and mice and of for and with
No takes yet. Share an insight, caveat, or question.
Wei et al. (2008) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: