Nuclear functions regulated by the VRK1 kinase

ABSTRACT

In the nucleus, the VRK1 Ser-Thr kinase is distributed in nucleoplasm and chromatin, where it has different roles. VRK1 expression increases in response to mitogenic signals. VRK1 regulates cyclin D1 expression at G0 exit and facilitates chromosome condensation at the end of G2 and G2/M progression to mitosis. These effects are mediated by the phosphorylation of histone H3 at Thr3 by VRK1, and later in mitosis by haspin. VRK1 regulates the apigenetic patterns of histones in processes requiring chromating remodeling, such as transcription, replication and DNA repair. VRK1 is overexpressed in tumors, facilitating tumor progression and resistance to genotoxic treatments. VRK1 also regulates the organization of Cajal bodies assembled on coilin, which are necessary for the assembly of different types of RNP complexes. VRK1 pathogenic variants cuase defects in Cajal bodies, functionally altering neurons with long axons and leading to neurological diseases, such as amyotrophic laterla sclerosis, spinal muscular atrophy, distal hereditay motor neuropathies and Charcot-Marie-Tooth.

KEYWORDS:

• Cajal bodies
• cell cycle
• chromatin
• DNA damage
• histones
• VRK1

Disclosure statement

No potential conflict of interest was reported by the author(s).

Abbreviations

VRK1	=	vaccinia related kinase 1
NHK-1	=	nucleosomal histone kinase-1
CB	=	Cajal body
ALS	=	amyotrophic lateral sclerosis
SMA	=	Spinal muscular atrophy
CMT	=	Charcot-Marie-Tooth
dHMN	=	distal hereditary motor neuropathy.
RNP	=	Ribonucleoprotein.
DDR	=	DNA damage response

Data availability statement

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Additional information

Funding

This research was funded by grants from Agencia Estatal de Investigación (doi: 10.13039/501100011033)-Ministerio de Ciencia, Innovación y Universidades-FEDER “Una manera de hacer Europa” (PID2019-105610RB-I00, PID2022-139598OB-I00).