日本研究人員日前發(fā)表論文說(shuō),，他們發(fā)現(xiàn)人體細(xì)胞核內(nèi)一種蛋白質(zhì)是阻礙肌體抑制癌癥的“路障”，如果能減少這種蛋白質(zhì)的量或減少其表達(dá),，癌癥發(fā)展就能得到一定程度的抑制,。
九州大學(xué)教授鈴木聰領(lǐng)導(dǎo)的科研小組在最新一期《自然—醫(yī)學(xué)》（Nature Medicine）雜志網(wǎng)絡(luò)版上發(fā)表論文說(shuō)，他們研究了人體細(xì)胞核內(nèi)的蛋白質(zhì)“PICT1”,，發(fā)現(xiàn)如果這種蛋白質(zhì)的量減少或表達(dá)被抑制,，另一種已知具有抑制癌癥作用的蛋白質(zhì)“p53”的量就會(huì)顯著增加。
研究人員針對(duì)癌癥患者進(jìn)行的病變組織分析顯示,，“PICT1”蛋白質(zhì)數(shù)量少或表達(dá)不活躍的癌癥患者,，5年生存率比這種蛋白質(zhì)數(shù)量多或表達(dá)活躍的患者要高。
研究發(fā)現(xiàn),，癌細(xì)胞中“PICT1”含量高的食道癌患者5年生存率為25%,，而“PICT1”含量低的患者5年生存率可達(dá)到42%；直腸癌患者癌細(xì)胞內(nèi)“PICT1”含量高和含量低的,，5年生存率分別為62%和81%,。
研究人員說(shuō)，本項(xiàng)成果有助于抗癌新藥的研發(fā),，以及進(jìn)行更準(zhǔn)確的癌癥復(fù)發(fā)預(yù)測(cè),。(生物谷 Bioon.com)
doi:10.1038/nm.2392
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Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11
Masato Sasaki; Kohichi Kawahara; Miki Nishio; Koshi Mimori; Ryunosuke Kogo; Koichi Hamada; Bunsho Itoh; Jia Wang; Yukako Komatsu; Yong Ryoul Yang; Hiroki Hikasa; Yasuo Horie; Takayuki Yamashita; Takehiko Kamijo; Yanping Zhang; Yan Zhu; Carol Prives; Toru Nakano; Tak Wah Mak; Takehiko Sasaki; Tomohiko Maehama; Masaki Mori; Akira Suzuki
PICT1 (also known as GLTSCR2) is considered a tumor suppressor because it stabilizes phosphatase and tensin homolog (PTEN), but individuals with oligodendrogliomas lacking chromosome 19q13, where PICT1 is located, have better prognoses than other oligodendroglioma patients. To clarify the function of PICT1, we generated Pict1-deficient mice and embryonic stem (ES) cells. Pict1 is a nucleolar protein essential for embryogenesis and ES cell survival. Even without DNA damage, Pict1 loss led to p53-dependent arrest of cell cycle phase G1 and apoptosis. Pict1-deficient cells accumulated p53, owing to impaired Mdm2 function. Pict1 binds Rpl11, and Rpl11 is released from nucleoli in the absence of Pict1. In Pict1-deficient cells, increased binding of Rpl11 to Mdm2 blocks Mdm2-mediated ubiquitination of p53. In human cancer, individuals whose tumors express less PICT1 have better prognoses. When PICT1 is depleted in tumor cells with intact P53 signaling, the cells grow more slowly and accumulate P53. Thus, PICT1 is a potent regulator of the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolus.
