Prothymosin α Interacts with Free Core Histones in the Nucleus of Dividing Cells

Abstract

The acidic protein prothymosin alpha (ProTalpha), with a broad presence in mammalian cells, has been widely considered to have a role in cell division, through an unrevealed mechanism in which histones may be involved in view of their ability to interact with ProTalpha in vitro. Results of co-immunoprecipitation experiments presented here demonstrate that ProTalpha interacts in vivo with core histones in proliferating B-lymphocytes (NC-37 cells). This interaction occurs with histones H3, H2A, H2B and H4 located free in the nucleoplasm, whereas no interaction was detected with histone H1, mono-nucleosome particles or chromatin. Moreover, the core histones form part of a nuclear multiprotein complex of about 700 kDa separated by ProTalpha-Sepharose affinity, with components including H3 and H4 acetyltranferases, H3 methyltransferases, hnRNP isotypes A3, A2/B1 and R, ATP-dependent and independent DNA helicases II, beta-actin and vimentin, all co-purifying by gel filtration. This indicates that the interaction of ProTalpha with core histones in the nucleus may be related to the structural modification of histones H3 and H4, and hence to chromatin activity, raising the possibility that the other proteins in the nuclear complex may play a role in this process.

Proinsulin C-peptide Regulates Ribosomal RNA Expression

“…Other studies have implicated acidic peptides in transcriptional regulation (17,18). One of them, prothymosin ␣, has been found to interact with free his-FIGURE 5.…”

“…tone proteins (18) and to modulate the interaction of histone H1 with chromatin (32). To study how C-peptide can stimulate rDNA transcription, we first investigated whether C-peptide interacts with histone extracts and observed that it had sequence-specific interactions with predominantly H4, but also H2B and S 18.…”

“…C-peptide lacks a nuclear localization signal and deviates from many intracrine factors by its very low pI, ϳ3.5. Previous studies have implicated acidic peptides in transcriptional regulation (17,18).…”

Possible novel roles of poly(rC)-binding protein 1 in SH-SY5Y neurocytes: an analysis using a dynamic Bayesian network

“…In addition to being a structural component of chromatin, histone H2AFX also maintains genomic stability and act as a multifunctional molecule [30] . The core histones form a nuclear multiprotein complex along with acetyltransferases, methyltransferases, hnRNPs, DNA helicase II, β-actin and vimentin, which may be associated with the structural modification of histones [31] . In addition,…”

Prothymosin-α Interacts with Mutant Huntingtin and Suppresses Its Cytotoxicity in Cell Culture

“…It has an unusual primary structure but lacks secondary structure (13). Although its function is still not well understood, current data suggest that ProT␣ facilitates cell proliferation and survival (14), remodeling of chromatin (15), and transcription (16). Previous in vitro studies have shown that ProT␣ is capable of preventing apoptotic cell death by inhibiting the formation of the apoptosome, a large cytosolic macromolecular complex formed in cells committed to programmed death (10).…”