title: A small ribosomal subunit (SSU) processome component, the human U3 protein 14A (hUTP14A) binds p53 and promotes p53 degradation.
abstract: Ribosome biogenesis is required for normal cell function, and aberrant ribosome biogenesis can lead to p53 activation. However, how p53 is activated by defects of ribosome biogenesis remains to be determined. Here, we identified human UTP14a as an SSU processome component by showing that hUTP14a is nucleolar, associated with U3 snoRNA and involved in 18 S rRNA processing. Interestingly, ectopic expression of hUTP14a resulted in a decrease and knockdown of hUTP14a led to an increase of p53 protein levels. We showed that hUTP14a physically interacts with p53 and functionally promotes p53 turn-over, and that hUTP14a promotion of p53 destabilization is sensitive to a proteasome inhibitor but independent of ubiquitination. Significantly, knockdown of hUTP14a led to cell cycle arrest and apoptosis. Our data identified a novel pathway for p53 activation through a defect in rRNA processing and suggest that a ribosome biogenesis factor itself could act as a sensor for nucleolar stress to regulate p53.
authors.affiliation: Department of Cell Biology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Lelin
authors.initials: L
authors.lastname: Hu
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Liangliang
authors.initials: L
authors.lastname: Zhang
authors.forename: Ruirui
authors.initials: R
authors.lastname: Kong
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Zheng
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Du
authors.forename: Yang
authors.initials: Y
authors.lastname: Ke
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology; D012337:RNA, Ribosomal, 18S / Q000096:biosynthesis / Q000235:genetics; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism; D020718:Ribonucleoproteins, Small Nucleolar / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D012337:RNA, Ribosomal, 18S; D020537:RNA, Small Nucleolar; C117378:RNA, U3 small nucleolar; D020718:Ribonucleoproteins, Small Nucleolar; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C117377:ribonucleoprotein, U3 small nucleolar; D046988:Proteasome Endopeptidase Complex