P15RS

Official Full Name

regulation of nuclear pre-mRNA domain containing 1A

Organism

Homo sapiens

GeneID

55197

Background

This gene encodes a cell-cycle and transcription regulatory protein. The encoded protein interacts with the cell cycle inhibitor cyclin-dependent kinase 4 inhibitor B and may function as a negative regulator of G(1)/S phase progression. This protein also forms homo- and hetrodimers with the protein, regulation of nuclear pre-mRNA domain-containing protein 1B, to form a scaffold that interacts with the C-terminal domain of RNA polymerase II subunit B1 and regulates several aspects of transcription. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 16. [provided by RefSeq, Dec 2014]

Synonyms

RPRD1A; P15RS; HsT3101;

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Detailed Information

P15RS and Wnt/β-Catenin Signaling

P15RS，a novel p15INK4b-related gene involved in G1/S progression，was identified by a differential display experiment from cells overexpressing P15INK4b，and regarded as a negative regulator in cell cycle control in G1 phase by down-regulating cyclin D1 expression. Wnt signaling is initiated by the binding of Wnt proteins to their receptors (Frizzled and LRP5/6) which branches into three distinct pathways, a Wnt-β-catenin pathway and two non-canonical pathways (Wnt-Ca²⁺ and Wnt-JNK). P15RS (a negative regulator of the cell cycle) blocks β-catenin-TCF4 complex formation and reduces Wnt signaling. Overexpression of P15RS reduces the interaction of β-catenin with TCF4, whereas the depletion of p15RS enhances their interaction. P15RS inhibits the Wnt signaling which initiates downstream gene expression by removing P15RS from promoters.

P15RS and Malignancy Inhibitory

P15RS is a ubiquitously expressed nuclear protein and regulated by P15, in turn, inhibits the expression of cyclin D and cyclin E. In a previous study, P15 was found to upregulate the expression of P15RS, which contains a CTD interacting domain (CID) that is present in the VHS/ENTH/ANTH superfamily of RNA processing proteins. In Xiaocui Zhang et al. study, while the P15RS expression had little effect on cell growth in monolayer cultures, it dramatically inhibited anchorage-independent cell growth in soft agar, a hallmark for malignancy. P15RS expression also inhibited cell migration and invasion which were key determinants of metastasis. Additionally, P15RS expression specifically downregulated the expression of cathepsin B and MMP-9 at RNA levels and promoted cell invasion through degrading extracellular matrix proteins. These results indicate that P15RS has malignancy-inhibitory functions independent of cell cycle inhibition and provides novel insight on the role of P15 in tumor inhibition.

References:

Yinyuan Wu, Yanquan Zhang, Haiwei Zhang, Xi Yang, Yinyin Wang, Fangli Ren, Huitu Liu, Yonggong Zhai, Baoqing Jia, Jun Yu and Zhijie Chang. (2010) 'p15RS Attenuates Wnt/β-Catenin Signaling by Disrupting β-Catenin﹒TCF4 Interaction', BIOLOGICAL CHEMISTRY, 285(10):34621-34631.
Chunxiao Liu, Yanquan Zhang, Jun Li, Yinyin，Wang, Fangli Ren, Yifan Zhou, Yinyuan Wu, Yarui Feng, Yu Zhou, Fuqin Su, Baoqing Jia，Dong Wang and Zhijie Chang. (2015) 'p15RS (p15INK4b Related Sequence)/RPRD1A (Regulation of Nuclear Pre-mRNA Domain-Containing Protein1A) Interacts with HDAC2 (Histone Deacetylase 2) in Inhibition of the Wnt/β-catenin Signaling Pathway', J. Biol. Chem, 290: 9701-9713.
XIAOCUI ZHANG, QIUJU CAO, XIAODAN LIU, SHUAISHUAI LIU, Juan Wang, SHENG SUN, OU WANG, ZHIHUA TIAN, HUITU LIU, JIAN KUANG and Wei Zhang. (2015) 'Cellular and molecular evidence for malignancy inhibitory functions of p15RS', Cell Cycle, 11(10): 1988-1998.

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