N-acetyl-D-glucosamine kinase interacts with dynein light-chain roadblock type 1 at Golgi outposts in neuronal dendritic branch points

ABSTRACTIn this study, we examined the requirement for host dynein adapter proteins such as dynein light chain 1 (DYNLL1), dynein light chain Tctex-type 1 (DYNLT1), and p150Gluedin early steps of human immunodeficiency virus type 1 (HIV-1) replication. We found that the knockdown (KD) of DYNLL1, but not DYNLT1 or p150Glued, resulted in significantly lower levels of HIV-1 reverse transcription in cells. Following an attempt to determine how DYNLL1 could impact HIV-1 reverse transcription, we detected the DYNLL1 interaction with HIV-1 integrase (IN) but not with capsid (CA), matrix (MA), or reverse transcriptase (RT) protein. Furthermore, by mutational analysis of putative DYNLL1 interaction motifs in IN, we identified the motifs52GQVD and250VIQD in IN as essential for DYNLL1 interaction. The DYNLL1 interaction-defective IN mutant HIV-1 (HIV-1INQ53A/Q252A) exhibited impaired reverse transcription. Through further investigations, we have also detected relatively smaller amounts of particulate CA in DYNLL1-KD cells or in infections with HIV-1INQ53A/Q252Amutant virus. Overall, our study demonstrates the novel interaction between HIV-1 IN and cellular DYNLL1 proteins and suggests the requirement of this virus-cell interaction for proper uncoating and efficient reverse transcription of HIV-1.IMPORTANCEHost cellular DYNLL1, DYNLT1, and p150Gluedproteins have been implicated in the replication of several viruses. However, their roles in HIV-1 replication have not been investigated. For the first time, we demonstrated that during viral infection, HIV-1 IN interacts with DYNLL1, and their interaction was found to have a role in proper uncoating and efficient reverse transcription of HIV-1. Thus, interaction of IN and DYNLL1 may be a potential target for future anti-HIV therapy. Moreover, while our study has evaluated the involvement of IN in HIV-1 uncoating and reverse transcription, it also predicts a possible mechanism by which IN contributes to these early viral replication steps.

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Differential expression of dynein light chain LC8 type 1 in cancers of the breast.

10.31219/osf.io/7qd93 ◽

2021 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Breast Cancer ◽

Differential Expression ◽

Light Chain ◽

Survival Data ◽

Normal Breast ◽

Differentially Expressed ◽

Dynein Light Chain ◽

Significant Differential Expression ◽

Primary Tumors

Breast cancer affects women at relatively high frequency (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding the dynein light chain LC8 type 1, DYNLL1, when comparing primary tumors of the breast to the tissue of origin, the normal breast. DYNLL1 was also differentially expressed in the tumor cells of patients with triple negative breast cancer. DYNLL1 mRNA was present at significantly higher quantities in tumors of the breast as compared to normal breast tissue. Analysis of human survival data revealed that expression of DYNLL1 in primary tumors of the breast was correlated with overall survival in patients with luminal B subtype cancer, demonstrating a relationship between correlation of primary tumor expression with recurrence-free survival based on molecular subtype. DYNLL1 may be of relevance to initiation, maintenance or progression of cancers of the female breast.

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