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Genetics. 2014 Feb;196(2):443-53. doi: 10.1534/genetics.113.159541. Epub 2013 Dec 13.

The novel zinc finger protein dASCIZ regulates mitosis in Drosophila via an essential role in dynein light-chain expression.

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  • 1Department of Anatomy and Neuroscience, University of Melbourne, Parkville 3010, Melbourne, Victoria, Australia.

Abstract

The essential zinc finger protein ASCIZ (also known as ATMIN, ZNF822) plays critical roles during lung organogenesis and B cell development in mice, where it regulates the expression of dynein light chain (DYNLL1/LC8), but its functions in other species including invertebrates are largely unknown. Here we report the identification of the Drosophila ortholog of ASCIZ (dASCIZ) and show that loss of dASCIZ function leads to pronounced mitotic delays with centrosome and spindle positioning defects during development, reminiscent of impaired dynein motor functions. Interestingly, similar mitotic and developmental defects were observed upon knockdown of the DYNLL/LC8-type dynein light chain Cutup (Ctp), and dASCIZ loss-of-function phenotypes could be suppressed by ectopic Ctp expression. Consistent with a genetic function of dASCIZ upstream of Ctp, we show that loss of dASCIZ led to reduced endogenous Ctp mRNA and protein levels and dramatically reduced Ctp-LacZ reporter gene activity in vivo, indicating that dASCIZ regulates development and mitosis as a Ctp transcription factor. We speculate that the more severe mitotic defects in the absence of ASCIZ in flies compared to mice may be due to redundancy with a second, ASCIZ-independent, Dynll2 gene in mammals in contrast to a single Ctp gene in Drosophila. Altogether, our data demonstrate that ASCIZ is an evolutionary highly conserved transcriptional regulator of dynein light-chain levels and a novel regulator of mitosis in flies.

KEYWORDS:

ATM substrate Chk2-interacting Zn2+ finger protein; Drosophila; development; dynein; mitosis

PMID:
24336747
[PubMed - indexed for MEDLINE]
PMCID:
PMC3914618
Free PMC Article
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