Prolyl isomerase Pin1 shares functional similarity with phosphorylated CTD interacting factor PCIF1 in vertebrate cells.
The carboxy-terminal domain (CTD) of the RNA polymerase II (Pol II) largest subunit undergoes reversible phosphorylation during transcription cycle. The phosphorylated CTD plays critical roles in coordinating transcription with chromatin modification and RNA processing by serving as a scaffold to recruit various proteins. Recently, we identified a novel human WW domain-containing protein PCIF1 as a phosphorylated CTD-interacting factor and demonstrated that PCIF1 negatively modulates Pol II activity in vivo. In the present study, to explore cellular functions of PCIF1, we generated PCIF1-deficient chicken DT40 cell lines. We observed significant up-regulation of WW domain-containing prolyl isomerase Pin1 in two independently established PCIF1-deficient mutant clones. As reconstitution of PCIF1 in the mutants did not reduce Pin1 expression, PCIF1 may not be a negative regulator of Pin1 expression. We assume that Pin1 over-expression might suppress defects caused by PCIF1 deficiency in DT40 cells. We furthermore compared PCIF1 and Pin1 for their functional properties and found that these two proteins exhibit most similar target specificity among other CTD-binding WW proteins, overlapping subcellular localization and comparative inhibitory effects on transcriptional activation by Pol II in human cultured cells. These results suggest that Pin1 may have overlapping cellular function with PCIF1 in vertebrate cells.
Yunokuchi
Izumi
I
Department of Molecular and Cellular Biology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan.
Fan
Hong
H
Iwamoto
Yu
Y
Araki
Chisato
C
Yuda
Masamichi
M
Umemura
Hiroyasu
H
Harada
Fumio
F
Ohkuma
Yoshiaki
Y
Hirose
Yutaka
Y
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D005786:Gene Expression Regulation; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012319:RNA Polymerase II / Q000737:chemistry / Q000378:metabolism*; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; C472862:PCIF1 protein, human; D012319:RNA Polymerase II; C410949:RNA polymerase II largest subunit; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase