Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Nov 21, 2019; 10(3): 44-64
Published online Nov 21, 2019. doi: 10.4331/wjbc.v10.i3.44
Complex interactomes and post-translational modifications of the regulatory proteins HABP4 and SERBP1 suggest pleiotropic cellular functions
Carolina Colleti, Talita Diniz Melo-Hanchuk, Flávia Regina Moraes da Silva, Ângela Saito, Jörg Kobarg
Carolina Colleti, Flávia Regina Moraes da Silva, Jörg Kobarg, Faculty of Pharmaceutical Sciences, University of Campinas, Campinas 13083-871, Brazil
Carolina Colleti, Talita Diniz Melo-Hanchuk, Flávia Regina Moraes da Silva, Jörg Kobarg, Institute of Biology, Departament of Biochemistry and Tissue Biology, University of Campinas, Campinas 13083-862, Brazil
Ângela Saito, Laboratório Nacional de Biociências, CNPEM, Campinas 13083-970, Brazil
Author contributions: Colleti C, Melo-Hanchuk TD, da Silva FRM, Saito  and Kobarg J performed the literature search, analyzed and interpreted the data, generated the figures, contributed different sections of the manuscript and collated the final version of the text together. All authors read, revised and approved the final version.
Supported by the “Conselho Nacional de Desenvolvimento Cientifico e Tecnológico”, Grant No. 302534/2017-2 and the “ Fundação de Amparo à Pesquisa do Estado de São Paulo” (FAPESP, Grant 2014/21700-3, to JK).
Conflict-of-interest statement: The authors declare no conflict -of-interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Jörg Kobarg, PhD, Full Professor, Faculty of Pharmaceutical Sciences, University of Campinas, Rua Monteiro Lobato 255, Bloco F, Sala 3, Campinas 13083-862, Brazil.
Telephone: +55-19-35211443
Received: July 5, 2019
Peer-review started: July 16, 2019
First decision: August 20, 2019
Revised: August 30, 2019
Accepted: October 15, 2019
Article in press: October 15, 2019
Published online: November 21, 2019

The 57 kDa antigen recognized by the Ki-1 antibody, is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7% identity and 67.4% similarity with serpin mRNA binding protein 1, which is also named CGI-55, or plasminogen activator inhibitor type-1-RNA binding protein-1, indicating that they might be paralog proteins, possibly with similar or redundant functions in human cells. Through the identification of their protein interactomes, both regulatory proteins have been functionally implicated in transcriptional regulation, mRNA metabolism, specifically RNA splicing, the regulation of mRNA stability, especially, in the context of the progesterone hormone response, and the DNA damage response. Both proteins also show a complex pattern of post-translational modifications, involving Ser/Thr phosphorylation, mainly through protein kinase C, arginine methylation and SUMOylation, suggesting that their functions and locations are highly regulated. Furthermore, they show a highly dynamic cellular localization pattern with localizations in both the cytoplasm and nucleus as well as punctuated localizations in both granular cytoplasmic protein bodies, upon stress, and nuclear splicing speckles. Several reports in the literature show altered expressions of both regulatory proteins in a series of cancers as well as mutations in their genes that may contribute to tumorigenesis. This review highlights important aspects of the structure, interactome, post-translational modifications, sub-cellular localization and function of both regulatory proteins and further discusses their possible functions and their potential as tumor markers in different cancer settings.

Keywords: Cancer, Cell signaling, Regulatory protein, Protein interactions, Post-translational modifications

Core tip: Intracellular hyaluronic acid binding protein 4 and serpin mRNA binding protein 1 are paralog human regulatory proteins that share 41% amino acid sequence identity. The characterization of their protein interactomes suggested their functional association with transcriptional regulation, mRNA metabolism and in the cell’s DNA damage and stress responses. Their complex post-translation modifications, involving phosphorylation, arginine methylation and SUMOylation, as well as their finely regulated sub-cellular localization in the nucleus and cytoplasm as well as in several cytoplasmic and nuclear granules suggest extensive functional regulation. This review discusses the functional and structural aspects and emerging roles of these regulatory proteins in human cancer.