Multifunctional human transcriptional coactivator protein PC4 is a substrate of Aurora kinases and activates the Aurora enzymes

Abstract

Positive coactivator 4 (PC4), a human transcriptional coactivator, is involved in diverse processes like chromatin organization and transcription regulation. It is hyperphosphorylated during mitosis, with unknown significance. For the first time, we demonstrate the function of PC4 outside the nucleus upon nuclear envelope breakdown. A fraction of PC4 associates with Aurora A and Aurora B and undergoes phosphorylation, following which PC4 activates both Aurora A and B to sustain optimal kinase activity to maintain the phosphorylation gradient for the proper functioning of the mitotic machinery. This mitotic role is evident in PC4 knockdown cells where the defects are rescued only by the catalytically active Aurora kinases, but not the kinase-dead mutants. Similarly, the PC4 phosphodeficient mutant failed to rescue such defects. Hence, our observations establish a novel mitotic function of PC4 that might be dependent on Aurora kinase-mediated phosphorylation.

Nonhistone human chromatin protein PC4 is critical for genomic integrity and negatively regulates autophagy

“…The role of histone modifications in autophagy has not been deciphered in great details; however, recent advances in the field, signify the role of the HDAC inhibitors like butyrate and suberoylanilide hydroxamic acid which enhanced autophagic cell death in various human cancer cell lines. Thus, there is increasing interest to look into histone hyperacetylation state and induction of autophagy . Here in this report we try to directly co relate the histone acetylation level to autophagy induction in absence of PC4.…”

Chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin

“…Nucleus–cytoplasm shuttling of the CPC is probably important in prophase regulation of chromatin and the nuclear envelope, and there are hints that the CPC is involved in nuclear pore reformation late in cytokinesis (Afonso et al. , 2014) and that the CPC phosphorylates nuclear proteins during mitosis (Dhanasekaran et al. , 2016).…”

The effect of phosphate ion on the ssDNA binding mode of MoSub1, a Sub1/PC4 homolog from rice blast fungus

“…In contrast, acetylation stimulates dsDNA binding activity, which can be blocked by phosphorylation. In addition, phosphorylation of PC4 inhibits its kinase inhibition activity and hyperphosphorylation mediated by Aurora kinase may play significant roles during mitosis . Similarly, phosphorylation plays crucial roles in the Sub1 process .…”

“…In addition, phosphorylation of PC4 inhibits its kinase inhibition activity 20 and hyperphosphorylation mediated by Aurora kinase may play significant roles during mitosis. 21 Similarly, phosphorylation plays crucial roles in the Sub1 process. 1,3,22,23 For example, the transcription mediated by RNA polymerase II (RNAPII) is highly regulated by phosphorylation.…”