Wimuttisuk W, West M, Davidge B, Yu K, Salomon A, Singer JD. Novel Cul3 binding proteins function to remodel E3 ligase complexes. BMC Cell Biology. 2014; 15:28. doi: 10.1186/1471-2121-15-28. [ PMC free article] [ PubMed] [ CrossRef] [ Google Scholar] Our wigs are cut and styled to suit you. Our team will use their experience and attention to detail to help you find the colour and cut that matches your face, skin tone, and overall style. All our wig fittings are done in our discreet dressing rooms, allowing you to confidently and privately find the right wig for you. Wig Rejuvenation Giniger E, Tietje K, Jan LY, Jan YN. Lola encodes a putative transcription factor required for axon growth and guidance in Drosophila. Development. 1994; 120:1385–1398. [ PubMed] [ Google Scholar] We thank the reviewer for the comments. First, the effect of wts overexpression has been analyzed in lola MARCM clones (Figure 7—figure supplement 2 in the revised manuscript). Interestingly, wts overexpression does not suppress ISC proliferation induced by lola mutant, indicating that endogenous Lola is regulated by Wts in ISCs. Next, despite that it is difficult to detect endogenous Lola protein by WB analysis due to the nature of the antibodies, a faint but distinct band was detected in Figure 6J (long exposure). Furthermore, endogenous Lola protein levels decreased in wts mutant clones (Figure 6—figure supplement 3C-D’’’) or when wts RNAi is expressed (Figure 6G-I), indicating that endogenous Lola proteins are under Wts regulation. Micchelli CA, Perrimon N. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature. 2006; 439:475–479. doi: 10.1038/nature04371. [ PubMed] [ CrossRef] [ Google Scholar]

Udan RS, Kango-Singh M, Nolo R, Tao C, Halder G. Hippo promotes proliferation arrest and apoptosis in the salvador/Warts pathway. Nature Cell Biology. 2003; 5:914–920. doi: 10.1038/ncb1050. [ PubMed] [ CrossRef] [ Google Scholar] Children's animation. Join Lola and Charlie, a brother and sister, as they deal with everyday topics. Lola does not want a haircut. More Singh SR, Mishra MK, Kango-Singh M, Hou SX. Generation and staining of intestinal stem cell lineage in adult midgut. Methods in Molecular Biology. 2012; 879:47–69. doi: 10.1007/978-1-61779-815-3_4. [ PMC free article] [ PubMed] [ CrossRef] [ Google Scholar] Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R, 1000 Genome Project Data Processing Subgroup The sequence alignment/Map format and SAMtools. Bioinformatics. 2009; 25:2078–2079. doi: 10.1093/bioinformatics/btp352. [ PMC free article] [ PubMed] [ CrossRef] [ Google Scholar]

Lin G, Xu N, Xi R. Paracrine wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature. 2008; 455:1119–1123. doi: 10.1038/nature07329. [ PubMed] [ CrossRef] [ Google Scholar] Lola is required for ISC proliferation and midgut homeostasis (A)Relative lola mRNA levels were analyzed by real-time PCR. Due to its important role in ISC proliferation and midgut homeostasis, Lola protein levels are expected to be under precise and delicate controls. Interestingly, Wts physically interacts with Lola and Lola protein levels are regulated by Wts both in vitro and in vivo. It has been proposed that Wts and Mats colocalize in the cytoplasm or at the cell cortex, thereby restricting Yki in the cytoplasm ( Dong et al., 2007; Oh and Irvine, 2008; Sun et al., 2015). Exceptions have been reported, however, that activated LATS1/2 (Wts in mammals) is accumulated in the nucleus, where it phosphorylates YAP (Yki in mammals) ( Li et al., 2014). Based on these observations, it is feasible to speculate that Wts translocates to the nucleus and interacts with Lola, therefore regulating Lola protein stability. Our cell culture data further indicate a possibility of Lola translocation into the cytoplasm, and Wts interacts with Lola both in cytoplasm and nucleus. Despite the possibility of Wts translocation into the nucleus (or Lola translocation into the cytoplasm), Wts is unlikely to regulate Lola stability via phosphorylation, an event happened for Yki in the cytoplasm based on our results that Wts kinase activity is not required for Wts-Lola interaction. Furthermore, Wts-Lola interaction is independent of Wts-Yki interaction and Wts-mediated Yki phosphorylation, demonstrating that Wts controls Yki and Lola activity via separate and distinct mechanisms.

Being the first trans woman on ANTM was groundbreaking because it allowed me to live my dreams as my most authentic self. Please keep in mind there were no offers for Time and Vanity Fair covers or reality shows or CNN interviews; it was more like people wanting to exploit me because of my perceived difference instead of my talent." Furthermore, Dref and SkpA mRNA levels were also elevated in wts x1 clonal midguts ( Figure 7—figure supplement 1F). Genetic interaction analysis between wts and Dref or SkpA showed that co-expression of SkpA or Dref RNAi in wts RNAi midguts dramatically reduced the increase in the GFP + and p-H3 + cell number ( Figure 7A, Figure 7—figure supplement 1E and G–H’), indicating that SkpA and Dref are both required for Wts function in midgut homeostasis. These results support our hypothesis that Wts stabilizes Lola such that SkpA and Dref expressions are transcriptionally suppressed, thereby restricting ISC proliferation. Sun S, Reddy BV, Irvine KD. Localization of hippo signalling complexes and warts activation in vivo. Nature Communications. 2015; 6:8402. doi: 10.1038/ncomms9402. [ PMC free article] [ PubMed] [ CrossRef] [ Google Scholar] Since a key message of the manuscript is that Wrts stabilizes Lola, Is Lola ever seen in the cytoplasm or is Warts ever seen in the nucleus? Where does the biochemical interaction between Wrts and Lola take place? Although the whole pathway cannot be resolved in a single paper, going a bit further in the molecular mechanism would increase the impact of the presented work.I'm always evolving, but meeting the president and being invited to speak at the White House was a huge honor. Speaking at the UN was an honor as well; however, I realize my journey is ever-changing and expanding. And I'm so grateful for it."

Given that Wts is a Serine/Threonine protein kinase, we next sought to determine if Lola is a Wts substrate and phosphorylated by Wts. Surprisingly, Lola exhibited no shift in molecular weight when analyzed by the phos-tag gels ( Figure 6E), suggesting that Wts interacts with Lola in a manner independent of phosphorylation. To further validate this conclusion, a construct expressing Wts KD (Wts K743R, a kinase dead form of Wts) ( Lai et al., 2005) was generated. Not only that Wts KD interacted with Lola by Co-IP ( Figure 6—figure supplement 2C), Wts KD stabilized Lola similarly as the wild-type Wts (data not shown). These results suggest that Wts kinase activity is not essential for binding to Lola and does not affect Lola protein stability. On the other hand, previous studies have suggested that Wts interacts and phosphorylates Yki ( Goulev et al., 2008; Huang et al., 2005; Oh and Irvine, 2008). In our hands, both total amount and the S168 phosphorylation level of Yki co-immunoprecipitated with Wts remained unaffected in the presence or absence of Fg-Lola, suggesting that Wts-Lola interaction does not affect Wts-Yki interaction and Wts-mediated Yki phosphorylation ( Figure 6—figure supplement 2D). Taken together, these results demonstrate that Wts binds to Lola directly to moderate its turnover rate, a process independent of Wts kinase activity, Lola DNA binding, Wts-Yki interaction, and Wts-mediated Yki phosphorylation. My time on ANTM gave me a foot in the door and shone an important light on what it was like to be a transgender woman going through my transition. I think my 'made it' moment comes every time I'm afforded the opportunity to showcase my talents. I will feel like I've officially made it when I can just be known as Isis King—not Isis King the transsexual." Gervais L, Bardin AJ. Tissue homeostasis and aging: new insight from the fly intestine. Current Opinion in Cell Biology. 2017; 48:97–105. doi: 10.1016/j.ceb.2017.06.005. [ PubMed] [ CrossRef] [ Google Scholar]Pantalacci S, Tapon N, Léopold P. The salvador partner hippo promotes apoptosis and cell-cycle exit in Drosophila. Nature Cell Biology. 2003; 5:921–927. doi: 10.1038/ncb1051. [ PubMed] [ CrossRef] [ Google Scholar]

Ferres-Marco D, Gutierrez-Garcia I, Vallejo DM, Bolivar J, Gutierrez-Aviño FJ, Dominguez M. Epigenetic silencers and notch collaborate to promote malignant tumours by rb silencing. Nature. 2006; 439:430–436. doi: 10.1038/nature04376. [ PubMed] [ CrossRef] [ Google Scholar] Guo T, Lu Y, Li P, Yin MX, Lv D, Zhang W, Wang H, Zhou Z, Ji H, Zhao Y, Zhang L. A novel partner of scalloped regulates hippo signaling via antagonizing Scalloped-Yorkie activity. Cell Research. 2013; 23:1201–1214. doi: 10.1038/cr.2013.120. [ PMC free article] [ PubMed] [ CrossRef] [ Google Scholar] Morgan NS, Skovronsky DM, Artavanis-Tsakonas S, Mooseker MS. The molecular cloning and characterization of Drosophila Melanogaster myosin-IA and myosin-IB. Journal of Molecular Biology. 1994; 239:347–356. doi: 10.1006/jmbi.1994.1376. [ PubMed] [ CrossRef] [ Google Scholar] When I look at myself in the mirror, I see a strong woman. Sometimes I can feel vulnerable, but when I look at myself and think of my journey, I remind myself that I am strong."Transgender people are the coolest, most beautiful, most intelligent, most powerful people in the world. Unfortunately, most people treat us like shit. As for me, I'm white, I'm college educated, I've got a solid support system, I've got a job and citizenship to a first-world country. Aside from being transgender, I couldn't be much more privileged. I feel like I've had to fight tooth and claw to get where I am, but in the grand scheme of things, my career was practically handed to me. I have an immense responsibility to use my platform to improve the lives of trans women, especially trans women of color. After me, you should go and talk to a trans woman of color, because they need a platform a lot more than the white girls do. At the end of the day, trans women can't catch a break. That's why so many of us are unemployed, suicidal, and isolated from our families. What do I want to accomplish in the transgender community? Food and shelter would be a great start, and the right to use toilets in peace. Legal protection from professional discrimination would be nice. Empathy from cisgender folks would be nice. I could go on, but let's start there." Yin M, Zhang L. Hippo signaling: a hub of growth control, tumor suppression and pluripotency maintenance. Journal of Genetics and Genomics. 2011; 38:471–481. doi: 10.1016/j.jgg.2011.09.009. [ PubMed] [ CrossRef] [ Google Scholar] The people who have inspired me most are the people who I've met throughout my years in the community. The people who are always there sharing my posts, liking my videos, replying or commenting. It's amazing how much motivation you can gain when others say that you've helped them be a better person. I look up to a lot of entrepreneurs, trans activists, and spiritual teachers." Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW, Jaenisch R, Brummelkamp TR. YAP1 increases organ size and expands undifferentiated progenitor cells. Current Biology. 2007; 17:2054–2060. doi: 10.1016/j.cub.2007.10.039. [ PubMed] [ CrossRef] [ Google Scholar] Why you should know her: Often cited as the first transgender supermodel, Lea was discovered by Givenchy designer Riccardo Tisci in 2010 and became his muse. She's since appeared in magazines and on runways around the world, as well as in the Italian version of Dancing With the Stars in 2013. In November 2014, she was named the face of Redken.