HID1 domain-containing protein 1 is required for normal cell proliferation in Schizosaccharomyces pombe

Abstract

HID1 domain-containing protein 1 (HID1) is a Golgi apparatus (GA) protein involved in the trafficking of cellular material. From reduced expression in cancer cell lines, it had been proposed to be a tumor suppressor in humans. In contrast, it is required for normal larval development of Caenorhabditis elegans, thereby raising an apparent contradiction for HID1 function regarding the inhibition or maintenance of cell proliferation. An extensive comparison of publicly available gene expression data revealed that HID1 transcript levels in cancer cell lines were not representative of those in primary tumors, and the gene is amplified in many primary tumors. These findings question the role for its expression to suppress cell proliferation. Subsequently, we employed the model S. pombe to explore the role of HID1 in cell proliferation. The knock-out mutant hid1{Delta} exhibited a reduced proliferation phenotype due to a prolonged lag-phase but, eventually, attained parent strain rates of apparent proliferation. RNAseq-based transcriptomics revealed that hid1{Delta} retained features of metabolically stressed cells with quiescence-like transcriptional regulation. A label-free proteomic analysis revealed a lack of various membrane proteins suggesting cells with compromised Golgi apparatus (GA) function. The inability of hid1{Delta} to grow on agar containing a standard minimal medium suggested a link to metabolic deficiency. These findings point to a hid1{Delta}-related perturbation in GA function that compromises cell recovery from metabolic change.